MULTIVIRUS-SPECIFIC T CELL COMPOSITIONS AND THEIR USE IN TREATING OR PREVENTING VIRAL INFECTION OR DISEASE IN SOLID ORGAN TRANSPLANT RECIPIENTS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, PCT Application No. PCT/US2022/029500 filed on May 16, 2022, U.S. Provisional Application No. 63/342,624 filed on May 16, 2022, U.S. Provisional Application No. 63/484,189 filed on February 9, 2023, and U.S. Provisional Application No. 63/484,992 filed on February 14, 2023 The contents of each of the aforementioned patent applications are incorporated herein by reference in their entireties.

TECHNICAL FIELD

[0002] Embodiments of the disclosure concern at least the fields of cell biology, molecular biology, immunology, and medicine.

BACKGROUND

[0003] In healthy, immunocompetent individuals, T cell immunity defends against viral infections. In transplant recipients, the use of potent immunosuppressive regimens (and subsequent associated immune compromise) leaves patients susceptible to severe viral infections and diseases. Viral infections are major causes of mortality and morbidity, and they have become leading etiologies for transplant-related mortality.

[0004] BK viremia is a polyomavirus that causes disease primarily in immunocompromised individuals. After primary infection, the virus remains latent in genitourinary cells. In immunosuppressed kidney transplant recipients, the virus can reactivate and cause tubulointerstitial nephritis, and in some cases, ureteral stenosis (Goldberg 2016). Kidney transplant recipients with BK virus infection have a high risk of nephropathy and graft loss. Nephropathy secondary to BKV infection occurs in up to 10% of transplant recipients (Jawdeh 2017) and is usually seen within the first year following transplantation. There are no US Food and Drug Administration (FDA)-approved therapies for BKV infection in kidney transplant recipients. The current best treatment consists of reduction in immunosuppression with close monitoring of allograft function; however, such immunosuppression reduction may expose kidney transplant recipients to the risk of graft rejection. [0005] The cellular immune response to BKV plays a critical role in the control of BK virus replication. Several immune parameters predict an increased risk of high-level BK viremia; these include a low pre-transplant CD4+ T cell count (DeWolfe 2017), indicators of T cell exhaustion such as T cells with lower production of protective cytokines and interferon (fFN)-y (Mueller 2011), and a lower number of BKV-specific polyfunctional CD8+ T cells (Schmidt 2014).

[0006] Thus, there is a need in the art for effective, safe methods for treating viral infection or disease (for example, BKV infection or disease) in solid organ transplant recipients. Embodiments of the present disclosure address this and other critical, longfelt needs.

SUMMARY OF THE EMBODIMENTS

[0007] The present disclosure provides virus-specific T-lymphocytes (VSTs) compositions and methods of using the same to treat or prevent viral infections.

[0008] In some aspects, the disclosure provides a method for treating or preventing BK viremia and/or BK disease in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia and/or BK disease in the subject. [0009] In any of the foregoing or related aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant. [0010] In any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy. In some aspects, BK disease is high or low levels of BK virus in the subject’s blood. In some aspects, BK disease includes high-grade or low-grade levels of BK virus in the subject’s blood. In some embodiments of any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy. In some embodiments, BK disease is high or low levels of BK virus in the subject’s blood. In some embodiments, BK disease includes highgrade or low-grade levels of BK virus in the subject’s blood.

[0011] In some aspects, the disclosure provides a method for treating or preventing viral infection or viral disease in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or viral disease in the subject.

[0012] In any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some embodiments of any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, intestinal transplant or vascular tissue transplant. In some embodiments, the SOT is a kidney transplant.

[0013] In any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). [0014] In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV) and/or human herpes virus 6 (HHV-6).

[0015] In any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about 5xl0 ⁶ VSTs to about IxlO ⁸ VSTs. In some aspects, the composition is administered to the subject at a dose of about 5xl0 ⁶ VSTs to about 2xl0 ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about 2xl0 ⁷ VSTs to about 8xl0 ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about 1.2xl0 ⁷ VSTs to about 5xl0 ⁷ VSTs. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 5xl0 ⁶ VSTs to about IxlO ⁸ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 5xl0 ⁶ VSTs to about 2xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 2xl0 ⁷ VSTs to about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 1.2xl0 ⁷ VSTs to about 5xl0 ⁷ VSTs.

[0016] In any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. In some aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs. In some aspects, the composition is administered to the subject at a dose of about 5xl0 ⁶ VSTs. In some aspects, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about 2xl0 ⁷ VSTs. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. In some embodiments, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 5xl0 ⁶ VSTs. In some embodiments, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 2xl0 ⁷ VSTs.

[0017] In some aspects, the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about 8xl0 ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about l.OxlO ⁸ VSTs. In some aspects, the composition is administered to the subject at a dose of about 1.2xl0 ⁸ VSTs. In some aspects, the composition is administered to the subject at a dose of about 1.4xl0 ⁸ VSTs. In some aspects, the composition is administered to the subject at a dose of about 1.6xl0 ⁸ VSTs. [0018] In some embodiments, the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about l.OxlO ⁸ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 1.2xl0 ⁸ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 1.4xl0 ⁸ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 1.6xl0 ⁸ VSTs.

[0019] In any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some aspects, the composition is administered to the subject every 14 days (± three days) for 12 weeks.

[0020] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some embodiments, the composition is administered to the subject every fourteen days (± three days) for 12 weeks. [0021] In any of the foregoing or related aspects, the composition is administered to the subject every seven days for three weeks. In some aspects, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 14 days for nine weeks. In some aspects, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 28 days for nine weeks. In some aspects, the composition is administered to the subject every seven days for 12 weeks. In some aspects, treatment period is 12 weeks. In some aspects, the composition is administered to the patient every 7 days (± three days). In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days). In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days). In some aspects, the composition is administered to the patient every 7 days. In some aspects, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 14 days. In some aspects, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 28 days. In some aspects, the composition is administered to the subject every 14 days for 12 weeks.

[0022] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days for three weeks. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 14 days for nine weeks. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 28 days for nine weeks. In some embodiments, the composition is administered to the subject every seven days for 12 weeks. In some embodiments, treatment period is 12 weeks. In some embodiments, the composition is administered to the patient every 7 days (± three days). In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days). In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days). In some embodiments, the composition is administered to the patient every 7 days. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 14 days. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 28 days. In some embodiments, the composition is administered to the subject every 14 days for 12 weeks.

[0023] In any of the foregoing or related aspects, the composition is administered to the patient until viral load is unquantifiable. In some aspects, unquantifiable levels of viral load are less than the lower limit of quantification (<LLOQ) by quantitative polymerase chain reaction (qPCR) assay. In some embodiments of any of the foregoing or related aspects, the composition is administered to the patient until viral load is unquantifiable. In some embodiments, unquantifiable levels of viral load are less than the lower limit of quantification (<LLOQ) by quantitative polymerase chain reaction (qPCR) assay.

[0024] In any of the foregoing or related aspects, the composition is administered in the absence of viral load in the patient. In some embodiments of any of the foregoing or related aspects, the composition is administered in the absence of viral load in the patient.

[0025] In any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by quantitative polymerase chain reaction (qPCR) assay. In some embodiments of any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by quantitative polymerase chain reaction (qPCR) assay.

[0026] In any of the foregoing or related aspects, the composition is administered about 2 weeks to about 4 weeks after transplantation. In some aspects, the composition is administered about 2 weeks after transplantation. In some aspects, the composition is administered about 4 weeks after transplantation. In some embodiments of any of the foregoing or related aspects, the composition is administered about 2 weeks to about 4 weeks after transplantation. In some embodiments, the composition is administered about 2 weeks after transplantation. In some embodiments, the composition is administered about 4 weeks after transplantation.

[0027] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of greater than the lower limit of quantification (>LLOQ) by quantitative polymerase chain reaction (qPCR) assay. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of greater than the lower limit of quantification (>LLOQ) by quantitative polymerase chain reaction (qPCR) assay.

[0028] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of greater than the lower limit of quantification (>LLOQ) to about 10,000,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of greater than the lower limit of quantification (>LLOQ) to about 10,000,000 copies/mL. [0029] In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load greater than the lower limit of quantification (LLOQ).

[0030] In any of the foregoing or related aspects, the lower limit of quantification is about 350 c/mL. In some embodiments of any of the foregoing or related aspects, the lower limit of quantification is about 350 c/mL.

[0031] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 350 copies/mL to about 10,000,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 350 copies/mL to about 10,000,000 copies/mL.

[0032] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 350 copies/mL to about 10,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 350 copies/mL to about 10,000 copies/mL.

[0033] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 10,000 copies/mL to about 10,000,000 copies/mL.

[0034] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 1,000 copies/mL to about 10,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 1,000 copies/mL to about 10,000 copies/mL.

[0035] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 10,000 copies/mL to about 50,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 10,000 copies/mL to about 50,000 copies/mL.

[0036] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of at least 1,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of at least 1,000 copies/mL.

[0037] In any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of at least 10,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of at least 10,000 copies/mL.

[0038] In any of the foregoing or related aspects, the viral load is measured by quantitation by quantitative polymerase chain reaction (qPCR) assay. In some aspects, the viral load is confirmed by testing prior to administration of the composition. In some embodiments of any of the foregoing or related aspects, the viral load is measured by quantitation by quantitative polymerase chain reaction (qPCR) assay. In some embodiments, the viral load is confirmed by testing prior to administration of the composition.

[0039] In any of the foregoing or related aspects, the viral infection or viral disease is BK viremia or a BK disease. In some aspects, the viral load is BK viral load. In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is BK viremia or a BK disease. In some embodiments, the viral load is BK viral load.

[0040] In any of the foregoing or related aspects, the VSTs for administration to a subject comprise an HL A type, wherein the HL A type:

(i) matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; or

(ii) matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles and, optionally, matches the HLA type of the subject on one or more alleles. [0041] In some embodiments of any of the foregoing or related aspects, the VSTs for administration to a subject comprise an HLA type, wherein the HLA type: (i) matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; or

(ii) matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles and, optionally, matches the HLA type of the subject on one or more alleles.

[0042] In any of the foregoing or related aspects, the matching alleles of the solid organ transplant donor and the patient are the same alleles. In some aspects, the matching alleles of the solid organ transplant donor and the patient are different alleles. In some aspects, the HLA alleles for matching comprise alleles HLA-A, HLA-B, HLA-DR, and/or HLA-DQ. In some embodiments of any of the foregoing or related aspects, the matching alleles of the solid organ transplant donor and the patient are the same alleles. In some embodiments, the matching alleles of the solid organ transplant donor and the patient are different alleles. In some embodiments, the HLA alleles for matching comprise alleles HLA-A, HLA-B, HLA- DR, and/or HLA-DQ.

[0043] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0044] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject

[0045] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0046] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0047] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0048] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0049] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0050] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0051] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0052] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0053] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0054] In any of the foregoing or related aspects, the concentration of the VSTs in the composition is about 2xl0 ⁷ cells per 2mL. In some embodiments of any of the foregoing or related aspects, the concentration of the VSTs in the composition is in some embodiments about 2xl0 ⁷ cells per 2mL.

[0055] In any of the foregoing or related aspects, the composition is administered to the subject by intravenous administration. In some aspects, the composition is administered to the subject by intravenous infusion. In some aspects, the composition is administered to the subject by via peripheral or central line. In some aspects, the composition is administered by slow push infusion. In some aspects, the composition is administered over about five minutes as a slow push infusion. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject by intravenous administration. In some embodiments, the composition is administered to the subject by intravenous infusion. In some embodiments, the composition is administered to the subject by via peripheral or central line. In some embodiments, the composition is administered by slow push infusion. In some embodiments, the composition is administered over about five minutes as a slow push infusion.

[0056] In any of the foregoing or related aspects, the method results in a reduction of load in the subject compared to the viral load of the subject prior to administration of the composition. In some aspects, the viral load is BK viral load. In some aspects, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments of any of the foregoing or related aspects, the method results in a reduction of load in the subject compared to the viral load of the subject prior to administration of the composition. In some embodiments, the viral load is BK viral load. In some embodiments, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more. [0057] In any of the foregoing or related aspects, the method results in a reduction of viral load by at least 50% relative to baseline viral load. In some embodiments of any of the foregoing or related aspects, the method results in some embodiments in a reduction of viral load by at least 50% relative to baseline viral load.

[0058] In any of the foregoing or related aspects, the method results in a reduction of viral load by > 1 logio viral copies/mL relative to baseline viral load. In some embodiments of any of the foregoing or related aspects, the method results in some embodiments in a reduction of viral load by > 1 logio viral copies/mL relative to baseline viral load.

[0059] In any of the foregoing or related aspects, the method results in a reduction of viral load below the lower limit of quantitation by qPCR assay. In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load below the lower limit of quantitation by qPCR assay. In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load to less than 10,000 copies/mL. In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load to less than 1,000 copies/mL.

[0060] In any of the foregoing or related aspects, the method results in a reduction of viral load in the subject compared to the BK viral load of a subject who received a placebo treatment. In some aspects, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some aspects, the method results in a reduction of viral load below the lower limit of quantitation. In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load in the subject compared to the BK viral load of a subject who received a placebo treatment. In some embodiments, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, the method results in a reduction of viral load below the lower limit of quantitation.

[0061] In any of the foregoing or related aspects, the method results in reduction of viral load to unquantifiable levels for about 8 weeks to about 12 weeks. In some embodiments of any of the foregoing or related aspects, the method results in some embodiments in reduction of viral load to unquantifiable levels for about 8 weeks to about 12 weeks.

[0062] In any of the foregoing or related aspects, the method results in reduction of viral load to unquantifiable levels for about 12 weeks to about 1 year. In some embodiments of any of the foregoing or related aspects, the method results in reduction of viral load to unquantifiable levels for about 12 weeks to about 1 year. [0063] In any of the foregoing or related aspects, unquantifiable levels of viral load are less than the lower limit of quantification (<LLOQ) by quantitative polymerase chain reaction (qPCR) assay. In some embodiments of any of the foregoing or related aspects, unquantifiable levels of viral load are less than the lower limit of quantification (<LLOQ) by quantitative polymerase chain reaction (qPCR) assay.

[0064] In any of the foregoing or related aspects, the method results in a stable viral load for at least 12 weeks in the subject. In some embodiments of any of the foregoing or related aspects, the method results in a stable viral load for at least 12 weeks in the subject.

[0065] In any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by qPCR assay. In some aspects, the viral load is BK viral load. In some embodiments of any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by qPCR assay. In some embodiments, the viral load is BK viral load. [0066] In any of the foregoing or related aspects, treatment results in VST persistence in the subject. In some aspects, VST persistence in the subject lasts for at least 24 weeks from baseline. In some aspects, VST persistence in the subject lasts for at least 12 weeks from baseline. In some aspects, VST persistence in the subject lasts for at least 4 weeks from baseline. In some aspects, VST persistence in the subject lasts for at least 12 weeks from the final administration of the composition.

[0067] In some embodiments of any of the foregoing or related aspects, treatment results in VST persistence in the subject. In some embodiments, VST persistence in the subject lasts for at least 24 weeks from baseline. In some embodiments, VST persistence in the subject lasts for at least 12 weeks from baseline. In some embodiments, VST persistence in the subject lasts for at least 4 weeks from baseline. In some embodiments, VST persistence in the subject lasts for at least 12 weeks from the final administration of the composition.

[0068] In any of the foregoing or related aspects, treatment results in circulating functional BK specific T cells. In some aspects, functional BK specific T cells circulate in the subject for at least 4 weeks from baseline. In some aspects, functional BK specific T cells circulate in the subject for at least 12 weeks from baseline. In some aspects, functional BK specific T cells circulate in the subject for at least 24 weeks from baseline. In some aspects, functional BK specific T cells circulate in the subject for at least 4 weeks after the BK viral load is reduced below the lower limit of quantitation. In some aspects, functional BK specific T cells circulate in the subject for at least 12 weeks after the BK viral load is reduced below the lower limit of quantitation. In some aspects, functional BK specific T cells circulate in the subject for at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation.

[0069] In some embodiments of any of the foregoing or related aspects, treatment results in circulating functional BK specific T cells. In some embodiments, functional BK specific T cells circulate in the subject for at least 4 weeks from baseline. In some embodiments, functional BK specific T cells circulate in the subject for at least 12 weeks from baseline. In some embodiments, functional BK specific T cells circulate in the subject for at least 24 weeks from baseline. In some embodiments, functional BK specific T cells circulate in the subject for at least 4 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, functional BK specific T cells circulate in the subject for at least 12 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, functional BK specific T cells circulate in the subject for at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation.

[0070] In any of the foregoing or related aspects, treatment results in circulating functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6. In some aspects, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 4 weeks from baseline. In some aspects, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 12 weeks from baseline. In some aspects, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 24 weeks from baseline. In some aspects, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 4 weeks after the BK viral load is reduced below the lower limit of quantitation. In some aspects, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 12 weeks after the BK viral load is reduced below the lower limit of quantitation. In some aspects, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation.

[0071] In some embodiments of any of the foregoing or related aspects, treatment results in circulating functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6. In some embodiments, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 4 weeks from baseline. In some embodiments, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 12 weeks from baseline. In some embodiments, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 24 weeks from baseline. In some embodiments, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 4 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 12 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, functional T cells specific for CMV, EBV, AdV, JCV, and/or HHV6 circulate in the subject for at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation.

[0072] In any of the foregoing or related aspects, the method results in a reduction or prevention of subsequent viral infections in the subject with one or more viruses. In some aspects, the one or more viruses are selected from the group consisting of CMV, EBV, AdV, JCV, and HHV6. In some embodiments of any of the foregoing or related aspects, the method results in a reduction or prevention of subsequent viral infections in the subject with one or more viruses. In some embodiments, the one or more viruses are selected from the group consisting of CMV, EBV, AdV, JCV, and HHV6.

[0073] In any of the foregoing or related aspects, the method results in a longer time of BK viremia remission compared to the BK viremia remission in a subject that received a placebo treatment. In some aspects, the BK viremia remission is the length of time from the clearance of BK viremia to reappearance of detectable BK viremia. In some embodiments of any of the foregoing or related aspects, the method results in a longer time of BK viremia remission compared to the BK viremia remission in a subject that received a placebo treatment. In some embodiments, the BK viremia remission is the length of time from the clearance of BK viremia to reappearance of detectable BK viremia.

[0074] In any of the foregoing or related aspects, the polyclonal population of VSTs comprises VSTs specific for BKV antigens VP1 and large T (LT). In some aspects, the VSTs specific for BKV antigens comprise specificity for JC virus (JCV) antigens. In some embodiments of any of the foregoing or related aspects, the polyclonal population of VSTs comprises VSTs specific for BKV antigens VP1 and large T (LT). In some embodiments, the VSTs specific for BKV antigens comprise specificity for JC virus (JCV) antigens.

[0075] In any of the foregoing or related aspects, the composition further comprises VSTs with specificity for one or more antigens from one or more of cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), and/or human herpes virus 6 (HHV-6). In some embodiments, the one or more EBV antigens are selected from LMP2, EBNA1, BZLF1, and a combination thereof; the one or more CMV antigens are selected from IE1, pp65, and a combination thereof; the one or more adenovirus antigens are selected from Hexon, Penton, and a combination thereof; and the one or more HHV6 antigens are selected from U90, U11, U14, and a combination thereof.

[0076] In some embodiments of any of the foregoing or related aspects, the composition further comprises VSTs with specificity for one or more antigens from one or more of cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), and/or human herpes virus 6 (HHV-6). In some embodiments, the one or more EBV antigens are selected from LMP2, EBNA1, BZLF1, and a combination thereof; the one or more CMV antigens are selected from IE1, pp65, and a combination thereof; the one or more adenovirus antigens are selected from Hexon, Penton, and a combination thereof; and the one or more HHV6 antigens are selected from U90, U11, U14, and a combination thereof.

[0077] In any of the foregoing or related aspects, the composition further comprises VSTs with specificity for JC virus (JCV). In some embodiments of any of the foregoing or related aspects, the composition further comprises VSTs with specificity for JC virus (JCV).

[0078] In any of the foregoing or related aspects, the composition is posoleucel, wherein posoleucel is a population of VSTs comprising specificity for: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14. In some embodiments of any of the foregoing or related aspects, the composition is posoleucel, wherein posoleucel is a population of VSTs comprising specificity for: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14. [0079] In any of the foregoing or related aspects, the VSTs are produced by culturing, in the presence of antigens or a portion thereof, mononuclear cells from a suitable donor. In some embodiments of any of the foregoing or related aspects, the VSTs are produced by culturing, in the presence of antigens or a portion thereof, mononuclear cells from a suitable donor. [0080] In any of the foregoing or related aspects, the VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; or (ii) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles and, optionally, matches the HLA type of the subject on one or more alleles. In some embodiments of any of the foregoing or related aspects, the VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; or (ii) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles and, optionally, matches the HLA type of the subject on one or more alleles. [0081] In some aspects, the matching alleles of the solid organ transplant donor and the patient are the same alleles. In some aspects, the matching alleles of the solid organ transplant donor and the patient are different alleles. In some aspects, the HLA alleles for matching comprise alleles HLA-A, HLA-B, HLA-DR, and/or HLA-DQ.

[0082] In any of the foregoing or related aspects, the culturing is in the presence of IL4 and IL7. In some embodiments of any of the foregoing or related aspects, the culturing is in the presence of IL4 and IL7.

[0083] In any of the foregoing or related aspects, the method is associated with an acceptable safety profile. In some aspects, the safety profile is determined by assessing one or more of treatment-emergent adverse events, changes in vital signs, physical examination, hematology blood tests, clinical chemistry blood tests, urinalysis, and electrocardiogram (ECG). In some embodiments of any of the foregoing or related aspects, the method is associated with an acceptable safety profile. In some embodiments, the safety profile is determined by assessing one or more of treatment-emergent adverse events, changes in vital signs, physical examination, hematology blood tests, clinical chemistry blood tests, urinalysis, and electrocardiogram (ECG).

[0084] In any of the foregoing or related aspects, the method results in a reduction in the incidence of recrudescent or new infections with one or more viruses compared to the incidence of recrudescent or new infections with the one or more viruses in a subject who received a placebo treatment. In some aspects, the one or more viruses are selected from the group consisting of CMV, EBV, AdV, JCV, and HHV6. In some embodiments of any of the foregoing or related aspects, the method results in a reduction in the incidence of recrudescent or new infections with one or more viruses compared to the incidence of recrudescent or new infections with the one or more viruses in a subject who received a placebo treatment. In some embodiments, the one or more viruses are selected from the group consisting of CMV, EBV, AdV, JCV, and HHV6.

[0085] In any of the foregoing or related aspects, the method prevents or reduces the development of one or more subsequent viral infections in the subject following administration of the composition. In some aspects, the one or more subsequent viral infections are selected from CMV, AdV, EBV, JCV, and HHV6. In some aspects, the method reduces the viral load of the one or more subsequent viral infections by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some aspects, the viral load is measured by quantitation of viremia by qPCR assay. In any of the foregoing or related aspects, the method further comprises monitoring the blood and/or urine of the subject for BKV, CMV, AdV, EBV, JCV, and/or HHV-6. In some aspects, the viral load of BKV, CMV, AdV, EBV, JCV, and/or HHV-6 is measured by quantitation of viremia by qPCR assay. [0086] In some embodiments of any of the foregoing or related aspects, the method prevents or reduces the development of one or more subsequent viral infections in the subject following administration of the composition. In some embodiments, the one or more subsequent viral infections are selected from CMV, AdV, EBV, JCV, and HHV6. In some embodiments, the method reduces the viral load of the one or more subsequent viral infections by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, the viral load is measured by quantitation of viremia by qPCR assay. In some embodiments of any of the foregoing or related aspects, the method further comprises monitoring the blood and/or urine of the subject for BKV, CMV, AdV, EBV, JCV, and/or HHV-6. In some embodiments, the viral load of BKV, CMV, AdV, EBV, JCV, and/or HHV- 6 is measured by quantitation of viremia by qPCR assay.

[0087] In any of the foregoing or related aspects, the method results in an improvement in the subject’s estimated glomerular filtration rate (eGFR) compared to the eGFR of the subject prior to administration of the composition, and/or compared to the eGFR of a subject who received a placebo treatment. In some aspects, the improvement in eGFR is an increase in eGFR of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the eGFR of the subject prior to administration of the composition and/or compared to the eGFR of a subject who received the placebo treatment. In some embodiments of any of the foregoing or related aspects, the method results in an improvement in the subject’s estimated glomerular filtration rate (eGFR) compared to the eGFR of the subject prior to administration of the composition, and/or compared to the eGFR of a subject who received a placebo treatment. In some embodiments, the improvement in eGFR is an increase in eGFR of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the eGFR of the subject prior to administration of the composition and/or compared to the eGFR of a subject who received the placebo treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable during treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 1 week following treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 2 weeks following treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 4 weeks following treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 6 weeks following treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 8 weeks following treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 10 weeks following treatment. In some embodiments, the subject’s estimated glomerular filtration rate (eGFR) remains stable for at least 12 weeks following treatment.

[0088] In any of the foregoing or related aspects, the method results in an improvement in the subject’s serum creatine levels compared to the serum creatine levels of the subject prior to administration of the composition, and/or compared to the serum creatine levels of a subject who received a placebo treatment. In some aspects, the improvement in serum creatine levels is an increase in serum creatine levels of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the serum creatine levels of the subject prior to administration of the composition and/or compared to the serum creatine levels of a subject who received the placebo treatment. In some embodiments of any of the foregoing or related aspects, the method results in an improvement in the subject’s serum creatine levels compared to the serum creatine levels of the subject prior to administration of the composition, and/or compared to the serum creatine levels of a subject who received a placebo treatment. In some embodiments, the improvement in serum creatine levels is an increase in serum creatine levels of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the serum creatine levels of the subject prior to administration of the composition and/or compared to the serum creatine levels of a subject who received the placebo treatment.

[0089] In any of the foregoing or related aspects, the subject has undetectable levels of urinary polyomavirus haufen prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject has undetectable levels of urinary polyomavirus haufen prior to treatment.

[0090] In any of the foregoing or related aspects, the subject has undetectable levels of urinary polyomavirus haufen during treatment. In some embodiments of any of the foregoing or related aspects, the subject has undetectable levels of urinary polyomavirus haufen during treatment. [0091] In any of the foregoing or related aspects, the subject has undetectable levels of urinary polyomavirus haufen for 12 weeks following treatment. In some embodiments of any of the foregoing or related aspects, the subject has undetectable levels of urinary polyomavirus haufen for 12 weeks following treatment.

[0092] In any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 2 GVHD during treatment. In some embodiments of any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 2 GVHD during treatment.

[0093] In any of the foregoing or related aspects, subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 2 GVHD for 12 weeks following treatment. In some embodiments of any of the foregoing or related aspects, subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 2 GVHD for 12 weeks following treatment.

[0094] In any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 1 GVHD during treatment. In some embodiments of any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 1 GVHD during treatment.

[0095] In any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 1 GVHD for 12 weeks following treatment. In some embodiments of any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 1 GVHD for 12 weeks following treatment.

[0096] In any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) prior to treatment.

[0097] In any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) during treatment. In some embodiments of any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) during treatment. [0098] In any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) for 12 weeks following treatment. In some embodiments of any of the foregoing or related aspects, the subject does not experience an episode of graft versus host disease (GVHD) for 12 weeks following treatment.

[0099] In any of the foregoing or related aspects, the subject does not have liver dysfunction prior to treatment. In any of the foregoing or related aspects, the subject does not have liver dysfunction during treatment. In any of the foregoing or related aspects, the subject does not have liver dysfunction for 12 weeks following treatment. In some aspects, the liver dysfunction is defined as (i) liver transaminases more than 5 times the upper limit of normal (ULN) reference and/or (ii) direct bilirubin levels more than two times the ULN reference. In some embodiments of any of the foregoing or related aspects, the subject does not have liver dysfunction prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject does not have liver dysfunction during treatment. In some embodiments of any of the foregoing or related aspects, the subject does not have liver dysfunction for 12 weeks following treatment. In some embodiments, the liver dysfunction is defined as (i) liver transaminases more than 5 times the upper limit of normal (ULN) reference and/or (ii) direct bilirubin levels more than two times the ULN reference.

[0100] In any of the foregoing or related aspects, the subject does not have renal dysfunction prior to treatment. In any of the foregoing or related aspects, the subject does not have renal dysfunction during treatment. In any of the foregoing or related aspects, the subject does not have renal dysfunction for 12 weeks following treatment. In some aspects, renal dysfunction is defined by an estimated glomerular filtration rate (eGFR) of < 20 mL/min/1.73m ² . In some embodiments of any of the foregoing or related aspects, the subject does not have renal dysfunction prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject does not have renal dysfunction during treatment. In some embodiments of any of the foregoing or related aspects, the subject does not have renal dysfunction for 12 weeks following treatment. In some embodiments, renal dysfunction is defined by an estimated glomerular filtration rate (eGFR) of < 20 mL/min/1.73m ² .

[0101] In any of the foregoing or related aspects, the method further comprises pre-treatment with an antihistamine and/or an analgesic. In some aspects, the antihistamine is diphenhydramine. In some aspects, analgesic is acetaminophen. In some aspects, the dose of diphenhydramine is about 0.25 to about 0.5 mg/kg. In some aspects, the dose of diphenhydramine administered to the subject does not exceed 25 mg. In some aspects, diphenhydramine is administered intravenously or orally. In some aspects, the dose of acetaminophen is about 5 to about 10 mg/kg. In some aspects, the dose of acetaminophen administered to the subject does not exceed 1000 mg. In some aspects, the acetaminophen is administered to the subject intravenously or orally. In some embodiments of any of the foregoing or related aspects, the method further comprises pre-treatment with an antihistamine and/or an analgesic. In some embodiments, the antihistamine is diphenhydramine. In some embodiments, analgesic is acetaminophen. In some embodiments, the dose of diphenhydramine is about 0.25 to about 0.5 mg/kg. In some embodiments, the dose of diphenhydramine administered to the subject does not exceed 25 mg. In some embodiments, diphenhydramine is administered intravenously or orally. In some embodiments, the dose of acetaminophen is about 5 to about 10 mg/kg. In some embodiments, the dose of acetaminophen administered to the subject does not exceed 1000 mg. In some embodiments, the acetaminophen is administered to the subject intravenously or orally.

[0102] In any of the foregoing or related aspects, the subject is not administered high-dose systemic corticorsteroids prior to treatment and/or the subject is not administered corticosteroids concurrently with treatment. In any of the foregoing or related aspects, the subject is not administered corticosteroids prior to treatment and/or the subject is not administered corticosteroids concurrently with treatment. In some aspects, the corticosteroid is prednisone. In some aspects, prednisone is not administered at a dose of greater than 0.5 mg/kg/day or equivalent. In some embodiments of any of the foregoing or related aspects, the subject is not administered high-dose systemic corticorsteroids prior to treatment and/or the subject is not administered corticosteroids concurrently with treatment. In some embodiments of any of the foregoing or related aspects, the subject is not administered corticosteroids prior to treatment and/or the subject is not administered corticosteroids concurrently with treatment. In some embodiments, the corticosteroid is prednisone. In some embodiments, prednisone is not administered at a dose of greater than 0.5 mg/kg/day or equivalent.

[0103] In any of the foregoing or related aspects, the subject has not been administered abatacept and/or belatacept within three months of screening. In some embodiments of any of the foregoing or related aspects, in some embodiments, the subject has not been administered abatacept and/or belatacept within three months of screening.

[0104] In any of the foregoing or related aspects, the subject has not been administered abatacept and/or belatacept within 28 days of screening. In some embodiments of any of the foregoing or related aspects, the subject has not been administered abatacept and/or belatacept within 28 days of screening.

[0105] In any of the foregoing or related aspects, the subject has not been administered antithymocyte globulin (ATG) in doses of >4.5 mg/kg, alemtuzumab, or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days of randomization. In some embodiments of any of the foregoing or related aspects, the subject has not been administered anti -thymocyte globulin (ATG) in doses of >4.5 mg/kg, alemtuzumab, or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days of randomization. [0106] In any of the foregoing or related aspects, the method further comprises administering mycofenolate mofetil (MMF) and/or a calcineurin inhibitor to the subject. In some embodiments of any of the foregoing or related aspects, the method further comprises administering mycofenolate mofetil (MMF) and/or a calcineurin inhibitor to the subject.

[0107] In any of the foregoing or related aspects, the method further comprises administering one or more antiviral agents to the subject. In some aspects, the one or more antiviral agents comprise foscamet or ganciclovir. In some embodiments of any of the foregoing or related aspects, the method further comprises administering one or more antiviral agents to the subject. In some embodiments, the one or more antiviral agents comprise foscarnet or ganciclovir.

[0108] In any of the foregoing or related aspects, the method further comprises immunosuppression reduction if (i) the subject’s BK viral load is about 350 copies/mL to about 10,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 10,000 copies/mL about 14 days after the initial determination of the BK viral load, or (ii) the subject’s Bk viral load prior to administration of the composition is about 10,000 copies/mL to about 10,000,000 copies/mL and the subject’s BK viral load has not changed or increased about 28 days after the initial determination of BK viral load. In some aspects, the immunosuppression reduction comprises a reduction in administration of MMF and/or a reduction in the administration of a calcineurin inhibitor.

[0109] In some embodiments of any of the foregoing or related aspects, the method further comprises immunosuppression reduction if (i) the subject’s BK viral load is about 350 copies/mL to about 10,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 10,000 copies/mL about 14 days after the initial determination of the BK viral load, or (ii) the subject’s Bk viral load prior to administration of the composition is about 10,000 copies/mL to about 10,000,000 copies/mL and the subject’s BK viral load has not changed or increased about 28 days after the initial determination of BK viral load. In some embodiments, the immunosuppression reduction comprises a reduction in administration of MMF and/or a reduction in the administration of a calcineurin inhibitor.

[0110] In any of the foregoing or related aspects, the composition has been assessed for cell concentration, viability, identity, phenotype, potency, endotoxin levels, mycoplasma levels, and sterility prior to administration to the subject. In some aspects, the composition is negative for bacteria, fungi, and mycoplasma. In some embodiments of any of the foregoing or related aspects, the composition has been assessed for cell concentration, viability, identity, phenotype, potency, endotoxin levels, mycoplasma levels, and sterility prior to administration to the subject. In some embodiments, the composition is negative for bacteria, fungi, and mycoplasma.

[OHl] In any of the foregoing or related aspects, the composition is provided in a vial comprising about 1.0 x 10 ⁷ VSTs/mL in a volume of about 0.5 mL to about 16 mL. In some embodiments of any of the foregoing or related aspects, the composition is provided in a vial comprising about 1.0 x 10 ⁷ VSTs/mL in a volume of about 0.5 mL to about 16 mL.

[0112] In any of the foregoing or related aspects, the composition is provided in a vial comprising about 1.0 x 10 ⁷ VSTs/mL in a volume of about 4 mL. In some embodiments of any of the foregoing or related aspects, the composition is provided in a vial comprising about 1.0 x 10 ⁷ VSTs/mL in a volume of about 4 mL.

[0113] In any of the foregoing or related aspects, the composition further comprises a pharmaceutically acceptable carrier. In some embodiments of any of the foregoing or related aspects, the composition further comprises a pharmaceutically acceptable carrier.

[0114] In any of the foregoing or related aspects, the method further comprises thawing the composition and administering the composition to the subject within 30 minutes of the completion of the thaw. In some embodiments of any of the foregoing or related aspects, the method further comprises thawing the composition and administering the composition to the subject within 30 minutes of the completion of the thaw.

[0115] In any of the foregoing or related aspects, the composition comprises T cells with specificity against at least one antigen from at least two different viruses. In some embodiments any of the foregoing or related aspects, the composition comprises T cells with specificity against at least one antigen from at least two different viruses. [0116] In any of the foregoing or related aspects, the composition comprises T cells with specificity against at least one antigen from at least 3, 4, or 5 different viruses. In some embodiments of any of the foregoing or related aspects, the composition comprises T cells with specificity against at least one antigen from at least 3, 4, or 5 different viruses.

[0117] In any of the foregoing or related aspects, the composition is administered intravenously. In some embodiments of any of the foregoing or related aspects, the composition is administered intravenously.

[0118] In some aspects, the disclosure provides a kit comprising a container comprising a pharmaceutical composition comprising: a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), and a pharmaceutically acceptable carrier, and instructions for treating or preventing a viral infection or viral disease in a human subject, wherein treatment comprises administration of the pharmaceutical composition by intravenous administration at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs.

[0119] In some aspects, the disclosure provides a kit comprising a container comprising a pharmaceutical composition comprising: a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), and a pharmaceutically acceptable carrier, and instructions for treating or preventing BK viremia in a human subject, wherein treatment comprises administration of the pharmaceutical composition by intravenous administration at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs.

[0120] In any of the foregoing or related aspects, the subject is the recipient of a solid organ transplant (SOT). In some aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, the subject is the recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some embodiments, the SOT is a kidney transplant.

[0121] In any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV), and/or human herpes virus 6 (HHV-6).

[0122] In any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs. In some aspects, the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs.

[0123] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every 14 days (± three days) for 14 weeks. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every 14 days for 14 weeks. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every 14 days (± three days). In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every 14 days.

[0124] In any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks.

[0125] In any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks.

[0126] In any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for 12 weeks.

[0127] In any of the foregoing or related aspects, the composition is administered to the subject weekly. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject weekly.

[0128] In any of the foregoing or related aspects, the population of VSTs comprises specificity for at least one antigen from one or more of BKV, CMV, AdV, EBV, and HHV6. In some embodiments of any of the foregoing or related aspects, the population of VSTs comprises specificity for at least one antigen from one or more of BKV, CMV, AdV, EBV, and HHV6.

[0129] In any of the foregoing or related aspects, the population of VSTs comprises specificity for at least one antigen selected from: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv) EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14. In some embodiments of any of the foregoing or related aspects, the population of VSTs comprises specificity for at least one antigen selected from: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv) EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14.

[0130] In any of the foregoing or related aspects, the population of VSTs targets at least two different viruses. In some embodiments of any of the foregoing or related aspects, the population of VSTs targets at least two different viruses.

[0131] In any of the foregoing or related aspects, the composition is posoleucel. In some embodiments of any of the foregoing or related aspects, the composition is posoleucel.

[0132] In some aspects, the disclosure provides a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) for use in treating or preventing BK viremia and/or BK disease in a subject in need thereof, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia and/or BK disease in the subject.

[0133] In any of the foregoing or related aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant. [0134] In any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy. In some aspects, BK disease is high or low levels of BK virus in the subject’s blood. In some embodiments of any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy. In some embodiments, BK disease is high or low levels of BK virus in the subject’s blood.

[0135] In some aspects, the disclosure provides a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) for use in treating or preventing viral infection or viral disease in a subject in need thereof, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or viral disease in the subject.

[0136] In any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some embodiments, the SOT is a kidney transplant.

[0137] In any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). [0138] In any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs.

[0139] In any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some aspects, the composition is administered to the patient every 7 days (± three days). [0140] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some embodiments, the composition is administered to the patient every 7 days (± three days).

[0141] In some aspects, the disclosure provides the use of a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) for the manufacture of a medicament for treating or preventing BK viremia and/or BK disease in a subject in need thereof, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia and/or BK disease in the subject.

[0142] In any of the foregoing or related aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant. [0143] In any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy. In some aspects, BK disease is high or low levels of BK virus in the subject’s blood. In some embodiments of any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy. In some embodiments, BK disease is high or low levels of BK virus in the subject’s blood.

[0144] In some aspects, the disclosure provides the use of a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) for the manufacture of a medicament for treating or preventing viral infection or viral disease in a subject in need thereof, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or viral disease in the subject. [0145] In any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some aspects, the SOT is a kidney transplant. In some embodiments of any of the foregoing or related aspects, in some embodiments, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some embodiments, the SOT is a kidney transplant.

[0146] In any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6). In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV) and/or human herpes virus 6 (HHV-6).

[0147] In any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some aspects, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some aspects, the composition is administered to the patient every 7 days (± three days). In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some embodiments, the composition is administered to the patient every 7 days (± three days). [0148] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is a recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0149] In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant.

[0150] In some aspects, the disclosure provides a method for reducing viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is a recipient of a solid organ transplant (SOT), thereby reducing viral load in the subject.

[0151] In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant.

[0152] In some embodiments of any of the foregoing or related aspects, the subject’s viral load at baseline is greater than the lower limit of quantification (LLOQ). In some embodiments, the LLOQ is about 350 copies/mL.

[0153] In some embodiments, the subject’s viral load at baseline is about 350 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject’s viral load at baseline is about 350 copies/mL to about 10,000 copies/mL. In some embodiments, the subject’s viral load at baseline is about 10,000 copies/mL to about 50,000 copies/mL. In some embodiments , the subject’s viral load at baseline is about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject’s viral load at baseline is at least 1,000 copies/mL. In some embodiments, the subject’s viral load at baseline is at least 10,000 copies/mL.

[0154] In some embodiments of any of the foregoing or related aspects, the viral load is cytomegalovirus (CMV) viral load, Adenovirus (AdV) viral load, Epstein-Barr virus (EBV) viral load, BK virus (BKV) viral load and/or human herpes virus 6 (HHV-6) viral load. In some embodiments of any of the foregoing or related aspects, the viral load is cytomegalovirus (CMV) viral load, Adenovirus (AdV) viral load, Epstein-Barr virus (EBV) viral load, BK virus (BKV) viral load, JC virus (JCV), and/or human herpes virus 6 (HHV-6) viral load.

[0155] In some embodiments of any of the foregoing or related aspects, the viral load is BK viral load.

[0156] In some embodiments of any of the foregoing or related aspects, the subject has CMV viremia or CMV viral disease, AdV viremia or AdV viral disease, EBV viremia or EBV viral disease, BK viremia or BK viral disease and/or HHV-6 viremia or HHV-6 viral disease.

[0157] In some embodiments of any of the foregoing or related aspects, the subject has BK viremia or BK viral disease.

[0158] In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load in the subject compared to the viral load of the subject prior to administration of the composition. [0159] In some embodiments of any of the foregoing or related aspects, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, the reduction in viral load is a reduction of the viral load by about 10%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 20%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 25%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 30%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 35%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 40%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 45%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 50%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 55%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 60%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 65%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 70%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 75%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 80%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 85%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 90%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 95%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 98%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 99%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 99% or greater.

[0160] In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load below the lower limit of quantitation. In some embodiments, the method results in a reduction of viral load in the subject compared to the viral load of a subject who received a placebo treatment.

[0161] In some embodiments of any of the foregoing or related aspects, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, the reduction in viral load is a reduction of the viral load by about 50%. In some embodiments, the reduction in viral load is a reduction of the viral load by about 90%. [0162] In some embodiments, the viral load is reduced to less than 1,000 copies/mL. In some embodiments, the viral load is reduced to less than 10,000 copies/mL.

[0163] In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load below the lower limit of quantitation.

[0164] In some embodiments of any of the foregoing or related aspects, the method results in reduction of viral load to unquantifiable levels for about 8 weeks to about 12 weeks. In some embodiments, the method results in reduction of viral load to unquantifiable levels for about 12 weeks to about 1 year. In some embodiments, the method results in a stable viral load for at least 12 weeks in the subject.

[0165] In some embodiments of any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by quantitative polymerase chain reaction (qPCR) assay. [0166] In some embodiments of any of the foregoing or related aspects, the viral load is confirmed by testing prior to administration of the composition.

[0167] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. [0168] In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some embodiments, the composition is administered to the subject every seven days for three weeks. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 14 days for nine weeks. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 28 days for nine weeks. [0169] In some embodiments, the composition is administered to the subject every seven days for 12 weeks. In some embodiments, the composition is administered to the subject every seven days. In some embodiments, the composition is administered to the subject every two weeks for fourteen weeks. In some embodiments, the composition is administered to the subject every two weeks. In some embodiments, the composition is administered to the subject every fourteen days for fourteen weeks. In some embodiments, the composition is administered to the subject every fourteen days.

[0170] In some embodiments, the composition is administered to the patient every 7 days (± three days). In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days). In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days). In some embodiments, the composition is administered to the patient every 7 days. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 14 days. In some embodiments, the composition is administered to the subject every seven days for three weeks, followed by administration to the subject every 28 days.

[0171] In some embodiments of any of the foregoing or related aspects, the composition is administered to the patient until viral load is unquantifiable. In some embodiments, unquantifiable levels of viral load are less than the lower limit of quantification (<LLOQ) by quantitative polymerase chain reaction (qPCR) assay.

[0172] In some embodiments of any of the foregoing or related aspects, the composition is administered in the absence of viral load in the patient.

[0173] In some embodiments of any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by quantitative polymerase chain reaction (qPCR) assay. [0174] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0175] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0176] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0177] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0178] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject by intravenous administration.

[0179] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject during a treatment period. In some embodiments, the treatment period is 12 weeks. In some embodiments, the treatment period is followed by a follow-up period. In some embodiments, the follow-up period is 12 weeks. In some embodiments, the treatment period and the follow-up period comprise 24 weeks.

[0180] In some embodiments of any of the foregoing or related aspects, viral load is measured at the end of the follow-up period.

[0181] In some embodiments of any of the foregoing or related aspects, viral load is reduced by about 50% to about 100% compared to baseline. In some embodiments, viral load is reduced by about 50% to about 90% compared to baseline. In some embodiments, viral load is reduced by at least 50% compared to baseline. In some embodiments, viral load is reduced by at least 90% compared to baseline.

[0182] In some embodiments of any of the foregoing or related aspects, the viral load at baseline is at least 10,000 copies/mL.

[0183] In some embodiments of any of the foregoing or related aspects, viral load is measured 24 weeks after the first administration of the composition.

[0184] In some embodiments of any of the foregoing or related aspects, viral load is reduced by about 50% to about 100% compared to baseline. In some embodiments, viral load is reduced by about 50% to about 90% compared to baseline. In some embodiments, viral load is reduced by at least 50% compared to baseline. In some embodiments, viral load is reduced by at least 90% compared to baseline.

[0185] In some embodiments of any of the foregoing or related aspects, the viral load at baseline is at least 10,000 copies/mL.

[0186] In some embodiments of any of the foregoing or related aspects, the viral load is measured by quantitation of viremia by quantitative polymerase chain reaction (qPCR) assay. [0187] In some embodiments of any of the foregoing or related aspects, the viral load is plasma viral load. In some embodiments of any of the foregoing or related aspects, the viral load is serum viral load.

[0188] In some embodiments of any of the foregoing or related aspects, the composition comprises VSTs with specificity for one or more antigens from one or more of BK virus, cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), and/or human herpes virus 6 (HHV-6).

[0189] In some embodiments of any of the foregoing or related aspects, the one or more BK virus antigens are selected VP1, Large T, and a combination thereof; the one or more EBV antigens are selected from LMP2, EBNA1, BZLF1, and a combination thereof; the one or more CMV antigens are selected from IE1, pp65, and a combination thereof; the one or more adenovirus antigens are selected from Hexon, Penton, and a combination thereof; and the one or more HHV6 antigens are selected from U90, U11, U14, and a combination thereof.

[0190] In some embodiments of any of the foregoing or related aspects, the composition comprises VSTs with specificity for JC virus (JCV).

[0191] In some embodiments of any of the foregoing or related aspects, the population of VSTs comprises specificity for at least one antigen selected from: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14.

[0192] In some embodiments of any of the foregoing or related aspects, the population of VSTs targets at least two different viruses.

[0193] In some embodiments of any of the foregoing or related aspects, the composition is posoleucel, wherein posoleucel is a population of VSTs comprising specificity for: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14.

[0194] In some embodiments of any of the foregoing or related aspects, the subject is receiving or received stable immunosuppression following the solid organ transplant.

[0195] In some embodiments of any of the foregoing or related aspects, the subject does not experience cytokine release syndrome during treatment.

[0196] In some embodiments of any of the foregoing or related aspects, the subject does not experience cytokine release syndrome for at least 12 weeks after treatment.

[0197] In some embodiments of any of the foregoing or related aspects, the subject does not experience an adverse event > Grade 3 during treatment.

[0198] In some embodiments of any of the foregoing or related aspects, the subject does not experience an adverse event > Grade 3 for at least 12 weeks after treatment. [0199] In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 1,000 copies/mL to about 5,000 copies/mL.

[0200] In some embodiments of any of the foregoing or related aspects, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a viral infection or viral disease, and wherein the viral infection or viral disease comprises plasma viral load of at least 5,000 copies/mL.

[0201] In some embodiments of any of the foregoing or related aspects, the method further comprises immunosuppression reduction if (i) the subject’s BK viral load is about 350 copies/mL to about 5,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 5,000 copies/mL about 14 days after the initial determination of the BK viral load, or (ii) the subject’s Bk viral load prior to administration of the composition is about 5,000 copies/mL to about 10,000,000 copies/mL and the subject’s BK viral load has not changed or increased about 28 days after the initial determination of BK viral load.

[0202] In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load by > 1 logio viral copies/mL relative to baseline viral load, or viral load is reduced to less than 1,000 copies/mL or less than 5,000 copies/mL.

[0203] In some embodiments of any of the foregoing or related aspects, the subject’s viral load at baseline is about 350 copies/mL to about 5,000 copies/mL.

[0204] In some embodiments of any of the foregoing or related aspects, the subject’s viral load at baseline is about 5,000 copies/mL to about 50,000 copies/mL. In some embodiments, the subject’s viral load at baseline is about 5,000 copies/mL to about 10,000,000 copies/mL. [0205] In some embodiments of any of the foregoing or related aspects, the subject’s viral load at baseline is at least 5,000 copies/mL. In some embodiments, the viral load at baseline is at least 5,000 copies/mL. In some embodiments, the viral load at baseline is at least 5,000 copies/mL.

[0206] In some embodiments of any of the foregoing or related aspects, the VSTs comprise:

(i) an HLA type that matches the HLA type of the solid organ transplant donor on more than 3 HLA alleles; or

(ii) an HLA type that matches the HLA type of the solid organ transplant donor on more than 3 HLA alleles and, optionally, matches the HLA type of the subject on one or more alleles.

[0207] In some embodiments of any of the foregoing or related aspects, the matching alleles of the solid organ transplant donor and the patient are the same alleles. In some embodiments, the matching alleles of the solid organ transplant donor and the patient are different alleles.

In some embodiments, the HLA alleles for matching comprise alleles HLA-A, HLA-B, HLA- DR, and/or HLA-DQ.

[0208] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject on day 1 and then every 14 days.

[0209] In some embodiments of any of the foregoing or related aspects, the treatment period is 12 weeks.

[0210] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0211] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0212] In some aspects, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0213] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject on day 1 and then every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0214] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject on day 1 and then every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0215] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject on day 1 and then every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0216] In some embodiments of any of the foregoing or related aspects, 7 doses of the composition are administered to the subject. In some embodiments of any of the foregoing or related aspects, 8 doses of the composition are administered to the subject.

[0217] In some aspects, the disclosure provides a method for treating BK viremia and/or BK disease in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the subject has a BK viral load at baseline at least 5,000 copies/mL, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia and/or BK disease in the subject.

[0218] In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant.

[0219] In some embodiments of any of the foregoing or related aspects, BK disease is BK virus-associated nephropathy.

[0220] In some aspects, the disclosure provides a method for treating a viral infection and/or viral disease in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the subject has a viral load at baseline of at least 5,000 copies/mL, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or viral disease in the subject.

[0221] In some embodiments of any of the foregoing or related aspects, the SOT is a heart transplant, lung transplant, liver transplant, pancreas transplant, trachea transplant, skin transplant, cornea transplant, or vascular tissue transplant. In some embodiments, the SOT is a kidney transplant.

[0222] In some embodiments of any of the foregoing or related aspects, the viral infection or viral disease is cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6).

[0223] In some aspects, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the subject’s viral load at baseline is at least 5,000 copies/mL, and wherein the subject is a recipient of a solid organ transplant (SOT), thereby reducing BK viral load in the subject.

[0224] In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant.

[0225] In some aspects, the disclosure provides a method for reducing viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the subject’s viral load at baseline is at least 5,000 copies/mL, and wherein the subject is a recipient of a solid organ transplant (SOT), thereby reducing viral load in the subject.

[0226] In some embodiments of any of the foregoing or related aspects, the SOT is a kidney transplant.

[0227] In some embodiments of any of the foregoing or related aspects, the viral load at base line is at least 10,000 copies/mL.

[0228] In some embodiments of any of the foregoing or related aspects, the viral load at base line is about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the viral load at base line is about 5,000 copies/mL to about 50,000 copies/mL.

[0229] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 2xl0 ⁷ VSTs to about 8xl0 ⁷ VSTs.

[0230] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l.lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xl0 ⁸ VSTs, or about 1.6xl0 ⁸ VSTs.

[0231] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about 2xl0 ⁷ VSTs.

[0232] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs.

[0233] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject at a dose of about 8xl0 ⁷ VSTs.

[0234] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks.

[0235] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. [0236] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for 12 weeks.

[0237] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for 6 weeks.

[0238] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for 7 weeks.

[0239] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for 8 weeks.

[0240] In some embodiments of any of the foregoing or related aspects, the composition is administered to the patient every 7 days (± three days).

[0241] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days).

[0242] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days).

[0243] In some embodiments of any of the foregoing or related aspects, the composition is administered to the patient until viral load is unquantifiable. In some embodiments, unquantifiable levels of viral load are less than the lower limit of quantification (<LLOQ) by quantitative polymerase chain reaction (qPCR) assay. In some embodiments, the viral load is measured by quantitation of viremia by quantitative polymerase chain reaction (qPCR) assay. [0244] In some embodiments of any of the foregoing or related aspects, the viral load is confirmed by testing prior to administration of the composition.

[0245] In some embodiments of any of the foregoing or related aspects, the composition is administered about 2 weeks to about 4 weeks after transplantation.

[0246] In some embodiments of any of the foregoing or related aspects, the composition is administered about 2 weeks after transplantation.

[0247] In some embodiments of any of the foregoing or related aspects, the composition is administered about 4 weeks after transplantation.

[0248] In some embodiments of any of the foregoing or related aspects, the composition is administered less than 2 years after transplantation.

[0249] In some embodiments of any of the foregoing or related aspects, the concentration of the VSTs in the composition is about 2xl0 ⁷ cells per 2mL. [0250] In some embodiments of any of the foregoing or related aspects, the composition is administered to the subject by intravenous administration. In some embodiments, the composition is administered to the subject by intravenous infusion. In some embodiments, the composition is administered to the subject by via peripheral or central line. In some embodiments, the composition is administered by slow push infusion. In some embodiments, the composition is administered over about five minutes as a slow push infusion.

[0251] In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load in the subject compared to the viral load of the subject prior to administration of the composition.

[0252] In some embodiments of any of the foregoing or related aspects, the viral load is BK viral load.

[0253] In some embodiments of any of the foregoing or related aspects, the reduction in viral load is a reduction of the viral load by about 10%, about 25%, about 50%, about 75%, about 90%, or more.

[0254] In some embodiments of any of the foregoing or related aspects, the method results in a reduction of viral load below the lower limit of quantitation by qPCR assay.

[0255] In some embodiments of any of the foregoing or related aspects, the subject is an adult subject.

[0256] In some embodiments of any of the foregoing or related aspects, the subject is a pediatric subject. In some embodiments, the pediatric subject weighs less than 40 Kg. In some embodiments, the pediatric subject is administered half a dose of any dose of a preceding claim.

BRIEF DESCRIPTION OF THE DRAWINGS

[0257] FIG. 1 depicts an exemplary scheme for the manufacture of Posoleucel.

[0258] FIG. 2 provides a graph showing the percentage of CD3+, CD4+, and CD8+ T cells in the generated Posoleucel cell lines administered to study participants.

[0259] FIG. 3 depicts the workflow of the CytoMatch solid organ transplant algorithm for HLA matching of Posoleucel with the transplanted organ as well as the patient.

[0260] FIG. 4 depicts the clinical trial study design comprising a screening period, a 12- week dosing period, and a 12-week follow-up period. N numbers shown in figure are based on an estimated 1 : 1 : 1 randomization, final enrollment for study included: Arm 1 N=20, Arm 2 N=22, Placebo N=19.

[0261] FIG. 5 provides a timeline of the study period and indicts treatment days and TCRseq sample collection days for Arm 1 and Arm 2 of the study.

[0262] FIG. 6A depicts interim study data showing the percentage of patients with Posoleucel persistence confirmed by TCR sequences at weeks 0, 4, 12, and 24 of the study. [0263] FIG. 6B depicts the percentage of patients with Posoleucel persistence confirmed by TCR sequences pre-infusion, at weeks 4-6, weeks 12-16, and weeks 22-24 (N = 35 patients), and stratified by patients treated under Arm 1 (Q1 d) and Arm 2 (Q28d).

[0264] FIGs. 7A-7D graphically depicts interim study data showing the (FIG. 7A) BK viral load LoglO (copies/mL) in the active treatment group (Arm 1/Q 14d), (FIG. 7B) BK viral load Log 10 (copies/mL) in the hybrid treatment group (Arm 2/Q28d), (FIG. 7C) LoglO change in BK viral load from baseline in the active treatment group (Arm 1/Q 14d), and (FIG. 7D) LoglO change in BK viral load from baseline in the hybrid treatment group (Arm 2/Q28d).

[0265] FIGs. 8A-8B depict the interim study data showing mean (FIG. 8A) and median (FIG. 8B) LoglO change in BK viral load from baseline.

[0266] FIG. 9 provides graphs depicting BK virus viral DNA (copies/mL) in patients with high viral load (>10,000 copies/mL) and stable immunosuppression (IS) prior to administration of placebo or Posoleucel (Pre) and at week 14 and week 24 after the first administration of placebo or Posoleucel. Dotted lines represent patients that did not respond to treatment at week 24.

[0267] FIG. 10 provides graphs depicting BK virus-specific spot-forming cells (SFC) as measured by IFNy ELISpot assay performed with PBMCs isolated from patients prior to and post-infusion. The patients analyzed and depicted were patients with high viral load (>10,000 copies/mL) and stable immunosuppression (IS). The timepoints depicted are prior to administration of placebo or Posoleucel (Pre) and peak SFC detected within 14 weeks and within 24 weeks after the first administration of placebo or Posoleucel. Dotted lines represent patients that did not reach > 1 Logio reduction by week 24.

[0268] FIGs. 11A-11C depict the event rate (“probability”) over time of patients reaching BK viral load decline of > 1 Logio after initial treatment with Posoleucel or placebo in all patients (FIG. 11A), or patients enrolled with low (350 to <10,000 copies) (FIG. 11B) or high (>10,000 copies/mL) (FIG. 11C) viral loads. Day 1 is the date of first dose. [0269] FIG. 12 provides a graph depicting the sum frequency of Posoleucel -derived T cell clones (based on TCR deep sequencing analysis) in patients with low (350 to <10,000 copies) or high (>10,000 copies/mL) viral loads and stable immunosuppression levels prior to infusion. The sum frequency of clones was consistently higher in patients in the high viral load sub-group at all timepoints assessed (week 4, week 12, or week 24 after the first administration of Posoleucel). In essence the graph shows persistence of Posoleucel in all patients evaluated (N = 33), but detection at a higher frequency in those with high viral load. [0270] FIG. 13 provides graphs depicting the percentage of CD3+, CD4+, and CD8+ T cells in Posoleucel cell lines administered to patients in the low (350 to <10,000 copies/mL) or high (>10,000 copies/mL) viral load subgroups. All of these patients had stable immunosuppression levels prior to infusion.

[0271] FIG. 14 provides graphs measuring the potency of the Posoleucel cell lines administered to patients on the clinical trial as assessed by IFNy ELISpot assay. The results shown depict the frequency of BKV-specific T cells [spot-forming cells (SFC)] within cells administered to all study participants (left panel) and stratified by patients with an initial low (350 to <10,000 copies/mL) (middle panel) or high (>10,000 copies/mL) viral load (right panel).

[0272] FIG. 15A provides a graph measuring baseline frequency of BKV-specific fFNy- producing SFC as measured by ELISpot assay in patients with low (350 to <10,000 copies/mL) viral load or and high (>10,000 copies/mL) viral load prior to treatment with Posoleucel.

[0273] FIG. 15B provides graphs measuring fold change from baseline of BKV-specific IFNy-producing SFC as measured by ELISpot assay in all patients (N=52) with stable immunosuppression (IS) prior to infusion and stratified by patients with stable IS and low (350 to <10,000 copies/mL) viral load or stable IS and high (>10,000 copies/mL) viral load treated with Posoleucel compared to placebo. In the stable IS/low viral load group the frequency of BK-specific T cells remained relatively similar in patients infused with Posoleucel or placebo. In contrast, in the stable IS/high viral load group, Posoleucel treated participants had greater increases in BKV IFNy+ T cells versus placebo during treatment. [0274] FIG. 15C provides a graph depicting fold change of peak ELISpot response through week 24 from pre-dose of BKV-specific IFNy-producing SFC. Data shown represents mean +/- SEM peak ELISpot data up to week 6 (Wk2-6), week 14 (Wk2-14) and week 24 (Wk2- 24) in patients with stable immunosuppression (IS) stratified by high (>10,000 copies/mL) viral load treated with Posoleucel compared to placebo.

[0275] FIG. 16 provides graphs measuring fold change from baseline of BKV-specific ZFNy- producing SFC as measured by ELISpot assay in all patients with stable immunosuppression (IS) prior to infusion and stratified by patients with low (350 to <10,000 copies/mL) or high (>10,000 copies/mL) viral load treated with Arm 1 (Q14d) or Arm 2 (Q28d) dosing schedules compared to placebo. Responders to treatment (> 1 log reduction or below lower limit of quantification (LLOQ)) are represented by an X.

[0276] FIG. 17 provides individual patient graphs showing BK viral DNA (copies/mL), and BKV-specific spot-forming cells (SFC/5xl0 ⁵ PBMC) from IFNy ELISpot assay over the study period in three individual patients treated with either Arm 1 (Q14d) (FIGs. 17 B-C) or Arm 2 (Q28d) (FIG. 17A). Timepoints at which Posoleucel persistence was confirmed (by TCR deep sequencing) are indicated by an asterix (*).

[0277] FIGs 18A-18C depict the event rate (“probability”) over time of patients reaching BK viral load decline of > 1 Logio after treatment with Posoleucel or placebo in all patients with stable immunosuppression (IS) and baseline BK viral load >5,000 cps/mL and less than two years after transplant (N=23) (FIG. 18A), or patients with stable immunosuppression (IS), a BK viral load of 5,000 to <10,000 copies/mL, and less than two years after transplant (N=6) (FIG. 18B), or patients with stable immunosuppression (IS), a BK viral load of >10,000 to 10,000,000 copies/mL and less than two years after transplant (N=17) (FIG. 18C). p value is based off the Log-Rank Test. Day 0 is the date of randomization into treatment groups.

[0278] FIG. 19 provides graphs showing the HLA matching and distribution of Posoleucel lines administered to patients and stratified by treatment group Q14d (Arm 1), Q28d (Arm 2), or all. Left panel shows the HLA matching of the infused PSL lines to the allograft (kidney) (T:VST) and right panel shows the HLA matching of the infused PSL lines to the patient (P:VST).

[0279] FIG. 20A provides a graph showing change from baseline in eGFR over time after treatment with Posoleucel (PSL) or placebo (PBO).

[0280] FIG. 20B provides a graph showing change from baseline in eGFR over time after treatment with placebo (PBO), Posoleucel Arml (Q14d), or Posoleucel Arm 2 (Q28d).

[0281] FIG. 21 depicts BK viral load (copies/mL) (peak viral load and viral load at the primary endpoint, wk 14, in a study performed in allogeneic hematopoietic stem cell transplant recipients) and functional BK-specific T cells in peripheral blood (measured by spot forming cells, SFC) prior to infusion and the peak SFC detected within the primary endpoint. This analysis was performed in allogeneic hematopoietic stem cell transplant recipients.

DETAILED DESCRIPTION

Definitions

[0282] As used herein, the use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” Some embodiments of the disclosure may consist of or consist essentially of one or more elements, method steps, and/or methods of the disclosure. It is contemplated that any method or composition described herein can be implemented with respect to any other method or composition described herein.

[0283] The term “about” when immediately preceding a numerical value means ± 0% to 10% of the numerical value, ± 0% to 10%, ± 0% to 9%, ± 0% to 8%, ± 0% to 7%, ± 0% to 6%, ± 0% to 5%, ± 0% to 4%, ± 0% to 3%, ± 0% to 2%, ± 0% to 1%, ± 0% to less than 1%, or any other value or range of values therein. For example, “about 40” means ± 0% to 10% of 40 (i.e., from 36 to 44).

[0284] The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.”

[0285] As used herein, the terms “comprise,” “comprising,” “includes,” “including,” “has,” “having,” “contains,” “containing,” “characterized by,” or any other variation thereof, are intended to encompass a non-exclusive inclusion, subject to any limitation explicitly indicated otherwise, of the recited components. For example, a composition and/or method that “comprises” a list of elements (e.g., components or features or steps) is not necessarily limited to only those elements (or components or features or steps), but may include other elements (or components or features or steps) not expressly listed or inherent to the composition and/or method.

[0286] As used herein, the phrases “consists of’ and “consisting of’ exclude any element, step, or component not specified. For example, “consist of’ or “consisting of’ used in a claim would limit the claim to the components, materials or steps specifically recited in the claim except for impurities ordinarily associated with therewith (i.e., impurities within a given component). When the phrase “consist of’ or “consisting of’ appears in a clause of the body of a claim, rather than immediately following the preamble, the phrase “consist of’ or “consisting of’ limits only the elements (or components or steps) set forth in that clause; other elements (or components) are not excluded from the claim as a whole.

[0287] The term “inhibit”, as used herein, refers to the ability of a composition, agent, or method herein to hinder, restrain, prevent, or impede the function, level, activity, infectivity or replication rate of a virus, infection, or disease described herein. The term “inhibit” is used interchangeably with “prevent”, “reduce”, and “block” in the context of the definition of inhibit.

[0288] The term “neutralize,” as used herein, refers to the ability of a composition, agent or method herein to render a virus ineffective.

[0289] The term “viral antigen” as used herein refers to an antigen that is protein in nature. In specific embodiments, a viral antigen is a coat protein.

[0290] Specific examples of viral antigen include at least antigens from virus selected from EBV, CMV, Adenovirus, BK, JC virus, HHV6, RSV, Influenza, Parainfluenza, Bocavirus, Coronavirus, Rhinovirus, LCMV, Mumps, Measles, human Metapneumovirus, Parvovirus B, Rotavirus, Merkel cell virus, herpes simplex virus, HPV, HIV, HTLV1, HHV8 and West Nile Virus, zika virus, Ebola. Specific examples of viral antigens include at least BK virus antigens VP1 and Large T (LT), CMV antigens IE1 and pp65, adenovirus antigens Hexon and Penton, EBV antigens LMP2, EBNA1, and BZLF1, and/or HHV6 antigens U90, U11, and U14.

[0291] The terms “virus-specific T cells” or “virus-specific T cell lines” or “multi-virus specific T cells” are used interchangeably herein to refer to polyclonal T cell lines that have specificity and potency against a virus or viruses of interest. As described herein, a viral antigen or several viral antigens are presented to native T cells in peripheral blood mononuclear cells and the native CD4 and CD8 T cell populations expand in response to said viral antigen(s). For example, a virus-specific T cell for EBV can recognize EBV, thereby expanding the T cells specific for EBV. In another example, a virus-specific T cell for adenovirus and BK can recognize both adenovirus and BK, thereby expanding the T cells specific for adenovirus and BK.

[0292] As used herein, the terms “patient” or “subject” are used interchangeably herein to refer to any mammal, including humans, domestic and farm or agricultural animals such as pigs, cattle and goats, and zoo, sports, and pet animals, such as dogs, horses, cats. In some embodiments, the mammal is human, including adults, children, and the elderly. In some embodiments, the subject is a human who has received a solid organ transplant. In some embodiments, the solid organ transplant is a transplant of kidney, liver, intestines, heart, lung, or pancreas. In some embodiments, the subject is a human who has received a kidney transplant. In some embodiments, the subject has received a kidney transplant and has detectable BK virus in the blood. As used herein, when a subject is stated to have “BK viremia,” the subject has detectable levels of BK virus in the blood. For example, a subject with BK viremia may be diagnosed with low/intermediate BK viremia, meaning that the subject has blood levels of BKV of about 1,000 to about 10,000 copies/mL. As another example, a subject with BK viremia may be diagnosed with higher-grade BK viremia, meaning that the subject has blood levels of BKV of greater than 10,000 copies/mL. As another example, a subject with BK viremia may be diagnosed with higher-grade BK viremia, meaning that the subject has blood levels of BKV of about 10,000 to about 50,000 copies/mL. As another example, a subject with BK viremia may be diagnosed with higher- grade BK viremia, meaning that the subject has blood levels of BKV of about 5,000 to about 10,000,000 copies/mL. As another example, a subject with BK viremia may be diagnosed with higher-grade BK viremia, meaning that the subject has blood levels of BKV of 5,000 to 10,000,000 copies/mL. In some embodiments, a subject with higher-grade BK viremia has BKV blood levels greater than 5,000 copies/mL. In some embodiments, a subject with higher-grade BK viremia has BKV blood levels greater than 10,000 copies/mL.

[0293] As used herein “viremia” refers to the presence of virus in the blood. In some embodiments, a subject described herein has BK viremia. In some embodiments, the presence of virus in the blood is used interchangeably with the presence of virus in plasma.

[0294] As used herein “viruria” refers to the presence of virus in the urine. In some embodiments, a subject described herein has BK viruria.

[0295] The terms “treat”, "treating", "treatment" and the like, as used herein, unless otherwise indicated, refers to reversing, alleviating, inhibiting the process of, or preventing the disease, disorder or condition to which such term applies, or one or more symptoms of such disease, disorder or condition and includes the administration of any of the compositions, pharmaceutical compositions, or dosage forms described herein, to prevent the onset of the symptoms or the complications, or alleviating the symptoms or the complications, or eliminating the disease, condition, or disorder. In some instances, treatment is curative or ameliorating. In some embodiments, treating means that the subject’s BK viremia is controlled and/or reduced. In some embodiments, treating means that the subject’s BK viremia is cleared. Clearance of BK viremia is referred to herein, in some embodiments, as “BKV remission.” In some embodiments, treating means that the incidence one or more new viral infections or reactivation of one or more latent viruses is prevented.

[0296] The terms “administering”, “administer”, “administration” and the like, as used herein, refer to any mode of transferring, delivering, introducing, or transporting a therapeutic agent to a subject in need of treatment with such an agent. Such modes include, but are not limited to, intraocular, oral, topical, intravenous, intraperitoneal, intramuscular, intradermal, intranasal, and subcutaneous administration.

[0297] As used herein, the term “randomization” refers to a process of randomizing a patient population into different treatment groups. Treatment groups can include any treatments described herein including placebo or treatment with a VST.

[0298] As used herein, the term “baseline” refers to a measurement or value prior to administration of a composition described herein.

Overview

[0299] A serious unmet medical need exists for patients experiencing viral infections and diseases such as BKV-associated nephropathy. Up to 10% of kidney transplant recipients will have BK plasma viral loads >10,000 copies/mL, a level that is predictive of an allograft biopsy indicating BK virus-associated nephropathy (Hirsch 2013; Bohl 2007; Schachtner 2015), which can progress to graft loss (Gardner 1984). Even with the best current treatments (principally immunosuppression reduction), many centers report allograft nephropathy, rejection, and graft failure more commonly than in non-BK viremic patients (Favi 2019; El- Husseini 2019; Sawinski 2015). There are no FDA- or European Medicines Agency- approved antiviral therapies for BK viremia or BK virus nephropathy in kidney transplant recipients.

[0300] The present disclosure provides restoration of T cell immunity against BK virus in kidney transplant recipients by the administration of ex vivo expanded, non-genetically modified, virus-specific T cells (VSTs) to control viral infections and eliminate symptoms. Without wishing to be bound by any theories, VSTs recognize and kill virus-infected cells via their native T cell receptor (TCR), which binds to major histocompatibility complex (MHC) molecules expressed on target cells that present virus-derived peptides. [0301] In some embodiments, patients with low to no pre-existing immunity to BK virus exhibit high BK viral load, and following infusion of virus specific T cells (e.g., Posolecucel) these patients in some embodiments experience in vivo expansion of functional BK-reactive T cells. In some embodiments, such high BK viral load patients exhibit greater expansion of functional BK-reactive T cells after administration of virus specific T cells (e.g., Posolecucel cells) than patients that exhibit pre-existing imminuty to BK virus. Without being bound by theory, it is believed that this may be due to in vivo stimulation of expansion of the introduced (e.g., Posoleucel cells) virus-specific T cells by the higher levels of viral load circulating in these high BK viral load patients.

[0302] In some embodiments, VSTs are produced from peripheral blood mononuclear cells (PBMCs) procured from healthy, pre-screened, seropositive donors, which are available as a partially HLA-matched “off-the-shelf’ product. In some embodiments, the VSTs as described herein respond to (or “are specific for”) at least BKV. In some embodiments, the VSTs as described herein are multivirus specific T cells that respond to BKV and one or more additional viruses. For example, in some embodiments, the VSTs as described herein respond to BKV and one or more of CMV, EBV, AdV, HHV-6, JCV, or any combination thereof. In some embodiments, the VSTs provided herein respond to BKV, CMV, EBV, AdV, and HHV-6. The VST compositions provided herein that respond to BKV, CMV, EBV, AdV, and/or HHV6, in some embodiments, are referred to as “Posoleucel”, “PSL”, “Viralym-M,” or “AVLR105.” The VST compositions provided herein that respond to BKV, CMV, EBV, AdV, JCV, and/or HHV6, in some embodiments, are referred to as “Posoleucel”, “PSL”, “Viralym-M,” or “AVLR105.” Such VST compositions have been shown to successfully treat viral infections in hematopoietic stem cell transplant recipients. To date, there is no data or publicly available information regarding the safety, efficacy, or appropriate dosing regimen for VSTs in the context of kidney transplant recipients, which are generally treated with higher levels of immunosuppression and are at high risk of persistent, dangerous BK viremia.

Generation of Pepmix Libraries

[0303] In some embodiments of the disclosure, a library of peptides is provided to peripheral blood mononuclear cells (PBMCs) ultimately to generate a polyclonal population of VSTs. In some embodiments, a library of peptides is provided to a population of mononuclear cells to generate a polyclonal population of VSTs. In some embodiments, the library comprises a mixture of peptides (“pepmixes”) that span part or all of the same antigen. Pepmixes utilized in the disclosure may be from commercially available peptide libraries made up of peptides that are 15 amino acids long and overlapping one another by 11 amino acids, in certain aspects. In some cases, they may be generated synthetically. Examples include those from JPT Technologies (Springfield, VA) or Miltenyi Biotec (Auburn, CA). In some embodiments, the peptides are at least 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 or more amino acids in length, for example, and in specific embodiments there is overlap of at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,

13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34 amino acids in length, for example. In some embodiments, the peptides are 7, 8, 9, 10, 11, 12, 13,

14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 or more amino acids in length. In some embodiments, the peptides overlap by at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34 amino acids in length. Methods for using a mixture of pepmixes to stimulate PBMCs and generate polyclonal populations of VSTs are provided for example, in U.S. Patent Publication Nos. US2018/0187152, WO2013/119947 and Tzannou et al., J Clin Oncol. 2017 Nov 1; 35(31): 3547-3557, each of which is incorporated herein by reference in its entirety. [0304] In some embodiments, the amino acids as used in the pepmixes have at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99, at least 99.9% purity, inclusive of all ranges and subranges therebetween. In some embodiments, the amino acids as used here in the pepmixes have at least 70% purity.

[0305] The mixture of different peptides may include any ratio of the different peptides, although in some embodiments each particular peptide is present at substantially the same numbers in the mixture as another particular peptide. The methods of preparing and producing pepmixes for multiviral cytotoxic T cells with broad specificity is described in US2018/0187152, which is incorporated by reference in its entirety.

Production of VSTs

[0306] In some embodiments, methods of producing a polyclonal population of VSTs comprise isolating mononuclear cells (MNCs), or having MNCs, isolated, from blood obtained from donors. In some embodiments, the MNCs are PBMCs. MNCs and PBMCs are isolated by using the methods known by a skilled person in the art. By way of examples, density centrifugation (gradient) (Ficoll-Paque) can be used for isolating PBMCs. In other example, cell preparation tubes (CPTs) and SepMate tubes with freshly collected blood can be used for isolating PBMCs.

[0307] In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor. In some embodiments, the mononuclear cells are peripheral blood mononuclear cells (PBMCs). In some embodiments, the mononuclear cells are isolated from umbilical cord blood. In some embodiments, the mononuclear cells are isolated from the spleen. In some embodiments, the mononuclear cells are isolated from bone marrow.

[0308] In some embodiments, the MNCs are PBMCs. By way of example, PBMC can comprise lymphocytes, monocytes, and dendritic cells. By way of example, lymphocytes can include T cells, B cells, and NK cells. In some embodiments, the MNCs as used herein are cultured or cryopreserved. In some embodiments, the process of culturing or cryopreserving the cells can include contacting the cells in culture with one or more antigens under suitable culture conditions to stimulate and expand virus-specific T cells. In some embodiments, the one or more antigen can comprise one or more viral antigen.

[0309] In some embodiments, the process of culturing or cryopreserving the cells can include contacting the cells in culture with one or more epitope from one or more antigen under suitable culture conditions. In some embodiments, contacting the MNCs or PBMCs with one or more antigen, or one or more epitope from one or more antigen, stimulate and expand a polyclonal population of virus-specific T cells from each of the respective donor’s MNCs or PMBCs. In some embodiments, the virus-specific T cell lines can be cryopreserved.

[0310] In some embodiments, the one or more antigen can be in the form of a whole protein. In some embodiments, the one or more antigen can be a pepmix comprising a series of overlapping peptides spanning part of or the entire sequence of each antigen. In some embodiments, the one or more antigen can be a combination of a whole protein and a pepmix comprising a series of overlapping peptides spanning part of or the entire sequence of each antigen.

[0311] In some embodiments, the culturing of the PBMCs or MNCs is in a vessel comprising a gas permeable culture surface. In one embodiment, the vessel is an infusion bag with a gas permeable portion or a rigid vessel. In one embodiment, the vessel is a GRex bioreactor. In one embodiment, the vessel can be any container, bioreactor, or the like, that are suitable for culturing the PBMCs or MNCs as described herein. [0312] In some embodiments, the PBMCs or MNCs are cultured in the presence of one or more cytokine. In some embodiments, the cytokine is IL4. In some embodiments, the cytokine is IL7. In some embodiments, the cytokine is IL4 and IL7. In some embodiments, the cytokine includes IL4 and IL7, but not IL2. In some embodiments, the cytokine can be any combinations of cytokines that are suitable for culturing the PBMCs or MNCs as described herein.

[0313] In some embodiments, culturing the MNCs or PBMCs can be in the presence of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more different pepmixes. Pepmixes, a plurality of peptides, comprise a series of overlapping peptides spanning part of or the entire sequence of an antigen. In some embodiments, the MNCs or PBMCs can be cultured in the presence of a plurality of pepmixes. In this instance, each pepmix covers at least one antigen that is different than the antigen covered by each of the other pepmixes in the plurality of pepmixes. In some embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more different antigens are covered by the plurality of pepmixes.

[0314] In some embodiments, the pepmix comprises 15 mer peptides. In some embodiments, the pepmix comprises peptides that are suitable for the methods as described herein. In some embodiments, the peptides in the pepmix that span the antigen overlap in sequence by 8 amino acids, 9 amino acids, 10 amino acids, 11 amino acids, 12 amino acids, 13 amino acids, 14 amino acids, 15 amino acids. In some embodiments, the peptides in the pepmix that span the antigen overlap in sequence by 11 amino acids.

[0315] In some embodiments, a polyclonal population of VSTs comprises 95% or more T cells within the population. For example, in a population of IxlO ⁶ VSTs, at least 95% of the cells in the population are T cells (i.e. at least 950,000 cells). In some embodiments at least 90% of the cells are CD3+ T cells. In some embodiments, a polyclonal population of VSTs comprises 96% or more T cells within the population. In some embodiments, a polyclonal population of VSTs comprises 97% or more T cells within the population. In some embodiments, a polyclonal population of VSTs comprises 98% or more T cells within the population. In some embodiments, a polyclonal population of VSTs comprises 99% or more T cells within the population. Polyclonal Virus-Specific T Cell Compositions

[0316] The present disclosure includes polyclonal virus-specific T cell compositions, generated from seropositive donors (e.g., selected via the donor selection methods disclosed herein), with specificity against clinically significant viruses. In some embodiments, the clinically significant viruses can include but are not limited to EB V, CMV, AdV, BKV and/or HHV6. In some embodiments, the clinically significant viruses can include but are not limited to EBV, CMV, AdV, BKV, HHV6, and JCV. In some embodiments, the clinically significant viruses can include but are not limited to EBV, CMV, AdV, BKV, and HHV6. [0317] In some embodiments, the BKV antigen is large T (LT) and/or VP1. In some embodiments, the BKV antigen is VP1. In some embodiments, the BKV antigen is LT. In some embodiments the BKV antigen is each of LT and VP1. In some embodiments, the CMV antigen is IE1 and/or pp65. In some embodiments, the CMV antigen is IE1. In some embodiments, the CMV antigen is pp65.In some embodiments, the AdV antigen is hexon and/or penton. In some embodiments, the AdV antigen is hexon. In some embodiments, the AdV antigen is penton. In some embodiments, the EBV antigen is LMP2, EBNA1, and/or BZLF1. In some embodiments, the EBV antigen is LMP2. In some embodiments, the EBV antigen is EBNA1. In some embodiments, the EBV antigen is BZLF1. In some embodiments, the HHV-6 antigen is U11, U14, and/or U90. In some embodiments, the HHV-6 antigen is Ul i. In some embodiments, the HHV-6 antigen is U14. In some embodiments, the HHV-6 antigen is U90. In some embodiments, the antigens include each of BKV LT, BKV VP1, CMV IE1, CMV pp65, AdV hexon, AdV penton, EBV LMP2, EBV EBNA1, EBV BZLF1, HHV-6 U11, HHV-6 U14, and HHV-6 U90.

[0318] The present disclosure provides a composition comprising a polyclonal population of antigen specific T cells. In some embodiments, the polyclonal population of antigen specific T cells can recognize a plurality of viral antigens. In some embodiments, the polyclonal population of antigen specific T cells can recognize two or more, or a plurality, of viral antigens from a single virus. For example, in some embodiments, the polyclonal population of antigen specific T cells can recognize two or more, or a plurality, of viral antigens from BK virus (BKV), cytomegalovirus (CMV) antigens, adenovirus (Adv) antigens, Epstein-Barr virus (EBV) antigens, human herpes virus 6 (HHV-6) antigens, and JC virus. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for one or more of BKV antigens, cytomegalovirus (CMV) antigens, adenovirus (Adv) antigens, Epstein-Barr virus (EBV) antigens, and human herpes virus 6 (HHV-6) antigens. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for JC virus (JCV).

[0319] In some embodiments, the polyclonal population of VSTs comprises VSTs specific for BKV antigens. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for BKV antigens VP1 and Large T. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for BKV antigen VP1. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for BKV antigen Large T. In some embodiments, the VSTs specific for BKV antigens comprise specificity for JC virus (JCV) antigens.

[0320] In some embodiments, the polyclonal population of VSTs comprises VSTs specific for Epstein-Barr virus (EBV) antigens. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for EBV antigens LMP2, EBNA1, and BZLF1, or any combination thereof. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for EBV antigen LMP2. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for EBV antigen EBNA1. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for EBV antigen BZLF1.

[0321] In some embodiments, the polyclonal population of VSTs comprises VSTs specific for CMV antigens. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for CMV antigens IE1 and pp65. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for CMV antigen IEL In some embodiments, the polyclonal population of VSTs comprises VSTs specific for CMV antigen pp65.

[0322] In some embodiments, the polyclonal population of VSTs comprises VSTs specific for AdV antigens. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for AdV antigens Hexon and Penton. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for AdV antigen Hexon. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for AdV antigen Penton.

[0323] In some embodiments, the polyclonal population of VSTs comprises VSTs specific for HHV6 antigens. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for HHV6 antigens U90, U11, and U14 or any combination thereof. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for HHV6 antigen U90. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for HHV6 antigen U11. In some embodiments, the polyclonal population of VSTs comprises VSTs specific for HHV6 antigen U14. [0324] In some embodiments, the polyclonal population of VSTs comprises specificity for one or more of BK virus antigen VP1, BK virus antigen Large T, AdV antigen Hexon, AdV antigen Penton, CMV antigen IE1, CMV antigen pp65, EBV antigen LMP2, EBV antigen EBNA1, EBV antigen BZLF1, HHV6 antigen U90, HHV6 antigen U11, HHV6 antigen U14, or any combination thereof.

[0325] In some embodiments, the composition comprising a polyclonal population of VSTs is Posoleucel. In some embodiments, Posoleucel is a population of VSTs comprising specificity for: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14.

[0326] In some embodiments, the Posoleucel population of VSTs is made from seropositive donor tissue by culturing PBMCs with IL4 and IL7 in presence of viral pepmixes (15-mer peptides overlapping by 11 amino acids (purity >90%) spanning the immunogenic antigens from: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14.

[0327] In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 1, 2, 3, 4, 5, or 6 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 1 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 2 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 3 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HL A type on 3 or more HL A alleles.

[0328] In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 1, 2, 3, 4, 5, or 6 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 1, 2, 3, 4, 5, 6, 7, or 8 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 1 allele. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 2 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 3 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 4 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 5 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 6 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 7 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 8 alleles.

[0329] In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 1 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on more than 3 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on more than 4 HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on more than 5 HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on more than 6 HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the solid organ transplant donor on more than 7 HLA alleles.

[0330] In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 1, 2, 3, 4, 5, 6, 7, or 8 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 1 allele. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 2 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 3 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 4 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 5 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 6 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 7 alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 8 alleles.

[0331] In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 1 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 2 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 3 or more HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 4 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 5 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 6 or more HLA alleles. In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on 7 or more HLA alleles.

[0332] In some embodiments, a polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient on more than 3 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient more than 4 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient more than 5 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient more than 6 HLA alleles. In some embodiments, polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the HLA type of the patient more than 7 HLA alleles.

[0333] In some embodiments, the HLA alleles for matching comprise alleles HLA-A, HLA- B, HLA-DR, and/or HLA-DQ. In some embodiments, the HLA alleles for matching comprise HLA-A alleles. In some embodiments, the HLA alleles for matching comprise HLA-B alleles. In some embodiments, the HLA alleles for matching comprise HLA-DR alleles. In some embodiments, the HLA alleles for matching comprise HLA-DQ alleles.

[0334] In some embodiments, the polyclonal population of VSTs are produced by culturing in the presence of IL4. In some embodiments, the polyclonal population of VSTs are produced by culturing in the presence of IL7. In some embodiments, the polyclonal population of VSTs are produced by culturing in the presence of IL4 and IL7. In some embodiments, the polyclonal population of VST’ s are stimulated with antigen (e.g., one or more pepmixes).

[0335] In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 2 or more HLA alleles in the presence of IL4. In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 2 or more HLA alleles in the presence of IL7. In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the patient’s HLA type on 2 or more HLA alleles in the presence of IL4 and IL7. In some embodiments, the polyclonal population of VST’s are stimulated with antigen (e.g., one or more pepmixes).

[0336] In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the solid organ transplant donor’s HLA type on 2 or more HLA alleles in the presence of IL4. In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the solid organ transplant donor’s HLA type on 2 or more HLA alleles in the presence of IL7. In some embodiments, the polyclonal population of VSTs are produced by culturing mononuclear cells from a donor having an HLA type that matches the solid organ transplant donor’s HLA type on 2 or more HLA alleles in the presence of IL4 and IL7. In some embodiments, the polyclonal population of VST’s are stimulated with antigen (e.g., one or more pepmixes).

[0337] In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles.

[0338] In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0339] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HL A alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 8 HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0340] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 7 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0341] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 6 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0342] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 5 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0343] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 4 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0344] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 3 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0345] In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 1 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 2 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 3 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 4 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 5 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 6 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 7 or more HLA alleles. In some embodiments, the polyclonal population of VSTs comprise: (i) an HLA type that matches the HLA type of the solid organ transplant donor on 2 or more HLA alleles; and (ii) an HLA type that matches the HLA type of the subject on 8 HLA alleles.

[0346] In some embodiments the polyclonal population of VSTs match on MHC class I alleles shared with the solid organ transplant donor. In some embodiments the polyclonal population of VSTs match on MHC class I alleles shared with the subject. In some embodiments the polyclonal population of VSTs match on MHC class II alleles shared with the solid organ transplant donor. In some embodiments the polyclonal population of VSTs match on MHC class II alleles shared with the subject. In some embodiments the polyclonal population of VSTs match on MHC class I alleles and MHC class II alleles shared with the solid organ transplant donor. In some embodiments the polyclonal population of VSTs match on MHC class I alleles and MHC class II alleles shared with the subject.

[0347] The present disclosure provides methods of treating BK viremia in a subject, comprising administering to a patient one or more suitable VST cell lines, either sequentially or simultaneously, described herein. The present disclosure provides methods of treating one of more of EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia in a subject, comprising administering to a patient one or more suitable VST cell lines, either sequentially or simultaneously, described herein. In some embodiments, the subject has received a solid organ transplant. In some embodiment, the solid organ transplant is a kidney, liver, intestine, heart, lung, or pancreas transplant. In some embodiments, the subject has received a kidney transplant.

[0348] In some embodiments, the product or composition comprising a population of VSTs provided herein is referred to as “Posoleucel” (also referred to herein as “PSL”, “ALVR105”, and “Viralym-M”). Posoleucel comprises VST specific for five viruses: EBV, CMB, AdV, BKV, and HHV6.

[0349] In some embodiments, the treatment efficacy is measured post-administration of the VST cell line. In other embodiments, the treatment efficacy is measured based on viremic resolution of infection. In other embodiments, the treatment efficacy is measured based on viruric resolution of infection. In other embodiments, the treatment efficacy is measured based on resolution of viral load in a sample from the patient. In other embodiments, the treatment efficacy is measured based on viremic resolution of infection, viruric resolution of infection, and resolution of viral load in a sample from the patient. In some embodiments, the treatment efficacy is measured by monitoring viral load detectable in the peripheral blood of the patient.

[0350] In some embodiments, the BK viremia is any BK viremia subtype (i.e., subtype I, II, III, or IV). In some embodiments, the BK viremia is BK viremia subtype I. In some embodiments, the BK viremia is BK viremia subtype II. In some embodiments, the BK viremia is BK viremia subtype III. In some embodiments, the BK viremia is BK viremia subtype IV. In some embodiments, the BK viremia is BK viremia subtype 1/a. In some embodiments, the BK viremia is BK viremia subtype 1/b-l. In some embodiments, the BK viremia is BK viremia subtype l/b-2. In some embodiments, the BK viremia is BK viremia subtype 1/c. In some embodiments, the BK viremia is BK viremia subtype 4/a-l. In some embodiments, the BK viremia is BK viremia subtype 4/a-2. In some embodiments, the BK viremia is BK viremia subtype 4/b-l. In some embodiments, the BK viremia is BK viremia subtype 4/b-2. In some embodiments, the BK viremia is BK viremia subtype 4/c-l. In some embodiments, the BK viremia is BK viremia subtype 4/c-2.

[0351] In some embodiments, the VSTs can be cultured ex vivo in the presence of both IL-7 and IL-4. In some embodiments, the multivirus VSTs have expanded sufficiently within 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days inclusive of all ranges and subranges therebetween, of culture such that they are ready for administration to a patient. In some embodiments, the multivirus VSTs have expanded sufficiently within any number of days that are suitable for the compositions ad described herein.

[0352] The present disclosure provides compositions comprising VSTs that exhibit negligible alloreactivity. In some embodiments, the compositions comprising CTL exhibit viability of greater than 70%.

[0353] In some embodiments, the compositions are negative for bacteria and fungi for at least 1 days, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days at least 7 days, at least 8 days, at least 9 days, at least 10 days, in culture. In some embodiments, the composition is negative for bacteria and fungi for at least 7days in culture.

[0354] In some embodiments, the compositions exhibit less than 1 EU/ml, less than 2 EU/ml, less than 3 EU/ml, less than 4 EU/ml, less than 5 EU/ml, less than 6 EU/ml, less than 7 EU/ml, less than 8 EU/ml, less than 9 EU/ml, less than 10 EU/ml of endotoxin. In some embodiments, the compositions exhibit less than 5 EU/ml of endotoxin. In some embodiments, the compositions are negative for mycoplasma.

[0355] In some embodiments, the pepmixes used for constructing the polyclonal of CTLs are chemically synthesized. In some embodiments, the pepmixes are optionally >10%, >20%, >30%, >40%, >50%, >60%, >70%, >80%, >90%, inclusive of all ranges and subranges therebetween, pure. In some embodiments, the pepmixes are optionally >90% pure.

[0356] In some embodiments, the VSTs are Thl polarized. In some embodiments, In some embodiments, the VSTs are able to lyse viral antigen-expressing targets cells. In some embodiments, the VSTs are able to lyse other suitable types of antigen-expressing targets cells. In some embodiments, the VSTs in the compositions do not significantly lyse non- infected autologous target cells. In some embodiments, the VSTs in the compositions do not significantly lyse non-infected autologous allogenic target cells.

[0357] The present disclosure provides methods of lysing a target cell comprising contacting the target cell with the compositions or pharmaceutical compositions as described herein. In some embodiments, the contacting between the target cell and the compositions or pharmaceutical compositions occurs in vivo in a subject. In some embodiments, the contacting between the target cell and the compositions or pharmaceutical compositions occurs in vivo via administration of the VSTs to a subject. In some embodiments, the subject is a human.

[0358] The present disclosure provides methods of treating or preventing a viral infection comprising administering to a subject in need thereof the compositions or the pharmaceutical compositions as described herein. In some embodiments, the amount of VSTs administered is about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs inclusive of all ranges and subranges therebetween. In some embodiments, the VSTs are administered to the subject. In some embodiments, the subject is immunocompromised. In some embodiments, the subject has acute myeloid leukemia. In some embodiments, the subject has acute lymphoblastic leukemia. In some embodiments, the subject has chronic granulomatous disease.

Compositions Comprising a Polyclonal Population of VSTs

[0359] In some embodiments, the disclosure provides a composition comprising a polyclonal population of VSTs. In some embodiments, the composition has been assessed for cell concentration, viability, identity, phenotype, potency, endotoxin levels, mycoplasma levels, and sterility prior to administration to the subject.

[0360] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for cell concentration prior to administration to the subject.

[0361] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for cell viability prior to administration to the subject. In some embodiments, viability is measured using Trypan blue dye exclusion assay.

[0362] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for cell identity prior to administration to the subject.

[0363] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for cell phenotype prior to administration to the subject. In some embodiments, cell phenotype is assayed by measuring CD3+, CD3+ TCR a [3 ,CD3+ TCR y 8 (T cells), CD3+CD4+ (T Inducer cells), CD3+CD8+, CD3+CD56+ (T cytotoxic cells), CD19+ (B cells), CD56+ CD3-, CD16+ CD3- (NK Cells), CD45BRT, CD14BRT (monocytes), or CD3-DR+CD83+ (DC cells).

[0364] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for potency prior to administration to the subject. In some embodiments, cell potency is measured by interferon gamma secretion assay (ELISPOT assay).

[0365] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for endotoxin levels prior to administration to the subject. In some embodiments, the composition is negative for endotoxins. In some embodiments, endotoxins are measured using Endosafe PTS.

[0366] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for mycoplasma levels prior to administration to the subject. In some embodiments, the composition is negative for mycoplasma. In some embodiments, mycoplasma is measured using Mycoalert (Lonza).

[0367] In some embodiments, the composition comprising a polycloncal population of VSTs has been assessed for sterility prior to administration to the subject. In some embodiments, the composition is negative for bacteria. In some embodiments, sterility is measured using one or more of Bactec Bacterial Sterility, Bactex Anarobi Sterility, CFR-modified Sterility, Bactec Fungal Sterility, and/or CFR-modified Fungal.

[0368] In some embodiments, the composition is negative for bacteria, fungi, and mycoplasma.

Dosing regimen

[0369] In some embodiments, the subject can have one or more medical conditions. In some embodiments, the subject receives a matched related donor transplant with reduced intensity conditioning prior to receiving the polyclonal population of VSTs. In some embodiments, the subject receives a matched unrelated donor transplant with myeloablative conditioning prior to receiving the polyclonal population of VSTs. In some embodiments, the subject receives a haplo-identical transplant with reduced intensity conditioning prior to receiving the polyclonal population of VSTs. In some embodiments, the subject receives a matched related donor transplant with myeloablative conditioning prior to receiving the polyclonal population of VSTs. In some embodiments, the subject has received a solid organ transplantation. In some embodiment, the solid organ transplant is a kidney, liver, intestine, heart, lung, or pancreas transplant. In some embodiments, the subject has received a kidney transplant. In some embodiments, the polyclonal population of VSTs compirses Posoleucel.

[0370] In some embodiments, the composition comprises about IxlO ⁶ , about 2xl0 ⁶ , about 3xl0 ⁶ , about 4xl0 ⁶ , about 5xl0 ⁶ , about 6xl0 ⁶ , about 7xl0 ⁶ , about 8xl0 ⁶ , about 9xl0 ⁶ , about IxlO ⁷ , about 1.5xl0 ⁷ about 2xl0 ⁷ , about 2.5xl0 ⁷ , about 3xl0 ⁷ , about 3.5xl0 ⁷ , about 4xl0 ⁷ , about 4.5xl0 ⁷ , about 5xl0 ⁷ , about 5.5xl0 ⁷ , about 6xl0 ⁷ , about 6.5xl0 ⁷ , about 7xl0 ⁷ , about 7.5xl0 ⁷ , about 8xl0 ⁷ , about 8.5xl0 ⁷ , about 9xl0 ⁷ , about IxlO ⁸ , about l. lxlO ⁸ , about 1.2xl0 ⁸ , about 1.3xl0 ⁸ , about 1.4xl0 ⁸ , about 1.5xl0 ⁸ , about 1.6xl0 ⁸ VSTs. In some embodiments, the composition comprises about IxlO ⁶ VSTs. In some embodiments, the composition comprises about 2xl0 ⁶ VSTs. In some embodiments, the composition comprises about 3xl0 ⁶ VSTs. In some embodiments, the composition comprises about 4xl0 ⁶ VSTs. In some embodiments, the composition comprises about 5xl0 ⁶ VSTs. In some embodiments, the composition comprises about 6xl0 ⁶ VSTs. In some embodiments, the composition comprises about 7xl0 ⁶ VSTs. In some embodiments, the composition comprises about 8xl0 ⁶ VSTs. In some embodiments, the composition comprises about 9xl0 ⁶ VSTs. In some embodiments, the composition comprises about IxlO ⁷ VSTs. In some embodiments, the composition comprises about 2xl0 ⁷ VSTs. In some embodiments, the composition comprises about 3xl0 ⁷ VSTs. In some embodiments, the composition comprises about 4xl0 ⁷ VSTs. In some embodiments, the composition comprises about 5xl0 ⁷ VSTs. In some embodiments, the composition comprises about 6xl0 ⁷ VSTs. In some embodiments, the composition comprises about 7xl0 ⁷ VSTs. In some embodiments, the composition comprises about 8xl0 ⁷ VSTs. In some embodiments, the composition comprises about 9xl0 ⁷ VSTs. In some embodiments, the composition comprises about IxlO ⁸ VSTs. In some embodiments, the composition comprises about 1. IxlO ⁸ VSTs. In some embodiments, the composition comprises about 1.2xl0 ⁸ VSTs. In some embodiments, the composition comprises about 1.3xl0 ⁸ VSTs. In some embodiments, the composition comprises about 1.4xl0 ⁸ VSTs. In some embodiments, the composition comprises about 1.5xl0 ⁸ VSTs. In some embodiments, the composition comprises about 1.6xl0 ⁸ VSTs. In some embodiments, the composition comprises Posoleucel.

[0371] In some embodiments, the subject has been diagnosed with high-grade BK viremia. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of at least about 10,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of about 10,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of 10,000 copies/mL or greater. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of greater than or equal to 10,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of greater than 10,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of at least about 5,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of about 5,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of 5,000 copies/mL or greater. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of greater than or equal to 5,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of greater than 5,000 copies/mL. In some embodiments, high-grade BK viremia is defined as a plasma BK viral load of greater than about 5,000 copies/mL, greater than about 6,000 copies/mL, greater than about 7,000 copies/mL, greater than about 8,000 copies/mL, greater than about 9,000 copies/mL, greater than about 10,000 copies/mL. As used herein, “high-grade” or “high” BK viremia refers to a viral load of at least 10,000 copies/mL. In some embodiments, “high-grade” or “high” BK viremia refers to a viral load of at least 5,000 copies/mL. As used herein, “low-grade” or “low” BK viremia refers to a viral load less than 10,000 copies/mL. In some embodiments, “low-grade” or “low” BK viremia refers to a viral load less than 5,000 copies/mL. In some embodiments, the subject has been diagnosed with high-grade BK viremia, wherein the highgrade BK viremia is defined as plasma BK viral load of at least about 5,000 copies/mL. In some embodiments, the subject has been diagnosed with high-grade BK viremia, wherein the high-grade BK viremia is defined as plasma BK viral load of at least about 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 20,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 30,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 40,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 50,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 100,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 10,000,000 copies/mL or greater. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of 5,000 copies/mL to 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 10,000 copies/mL and about 20,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 10,000 copies/mL and about 30,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 10,000 copies/mL and about 40,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 10,000 copies/mL and about 50,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 10,000 copies/mL and about 100,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 20,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 30,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between of 10,000 copies/mL to about 40,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 40,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 50,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 10,000,000 copies/mL or greater. In some embodiments, the subject has a plasma BK viral load of 10,000 copies/mL to 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 100,000 copies/mL to about 10,000,000 copies/mL.

[0372] In some embodiments, the subject has been diagnosed with low-grade BK viremia. In some embodiments, low-grade BK viremia is defined as a plasma BK viral load of less than 5,000 copies/mL. In some embodiments, low-grade BK viremia is defined as a plasma BK viral load of less than 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 5,000 copies/mL and about 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 1,000 copies/mL and about 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load between about 1,000 copies/mL and about 5,000 copies/mL.

[0373] In some embodiments, the subject has a plasma BK viral load of about 350 copies/mL to about 5,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 350 copies/mL to about 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 350 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 1,000 copies/mL to about 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 350 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 500 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 1,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 20,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 30,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 40,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 50,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 60,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 70,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 80,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 90,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 100,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 250,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 500,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 750,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 1,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 5,000,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of about 10,000,000 copies/mL. [0374] In some embodiments, the subject has a plasma BK viral load of at least 1,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 2,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 3,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 4,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 5,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 6,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 7,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 8,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 9,000 copies/mL. In some embodiments, the subject has a plasma BK viral load of at least 10,000 copies/mL.

[0375] In some embodiments, the subject has been diagnosed with one or more of high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia. In some embodiments, high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia is defined as a plasma viral load of at least about 5,000 copies/mL. In some embodiments, high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia is defined as a plasma viral load of about 5,000 copies/mL. In some embodiments, the subject has been diagnosed with high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia, wherein the high-grade viremia is defined as plasma viral load of at least about 5,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 5,000 copies/mL to about 10,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 5,000 copies/mL to about 10,000 copies/mL or greater. In some embodiments, the subject has been diagnosed with one or more of high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia. In some embodiments, high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia is defined as a plasma viral load of at least about 10,000 copies/mL. In some embodiments, high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia is defined as a plasma viral load of about 10,000 copies/mL. In some embodiments, the subject has been diagnosed with high-grade EBV, CMV, AdV, BKV, JCV and/or HHV6 viremia, wherein the high-grade viremia is defined as plasma viral load of at least about 10,000 copies/mL. In some embodiments, the subject has a plasma viral load between about 10,000 copies/mL and about 20,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL to about 20,000 copies/mL. In some embodiments, the subject has a plasma viral load between about 10,000 copies/mL and about 30,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL to about 30,000 copies/mL. In some embodiments, the subject has a plasma viral load between about 10,000 copies/mL and about 40,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL to about 40,000 copies/mL. In some embodiments, the subject has a plasma viral load between about 10,000 copies/mL and about 50,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL to about 50,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL to about 10,000,000 copies/mL. [0376] In some embodiments, the subject has a plasma viral load of about 350 copies/mL to about 5,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 350 copies/mL to about 10,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 350 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 1,000 copies/mL to about 10,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 350 copies/mL. In some embodiments, the subject has a plasma viral load of about 500 copies/mL. In some embodiments, the subject has a plasma viral load of about 1,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 5,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 20,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 30,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 40,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 50,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 60,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 70,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 80,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 90,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 100,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 250,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 500,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 750,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 1,000,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 5,000,000 copies/mL. In some embodiments, the subject has a plasma viral load of about 10,000,000 copies/mL.

[0377] In some embodiments, the subject has a plasma viral load of at least 1,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 2,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 3,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 4,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 5,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 6,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 7,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 8,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 9,000 copies/mL. In some embodiments, the subject has a plasma viral load of at least 10,000 copies/mL.

[0378] In some embodiments, the present disclosure provides pharmaceutical compositions comprising the compositions as described herein formulated for intravenous delivery. In some embodiments, the composition comprises Posoleucel.

[0379] In some embodiments, the composition as described herein is negative for bacteria. In some embodiments, the composition as described herein is negative for fungi. In some embodiments, the composition as described herein is negative for bacteria or fungi for at least 1 days, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, in culture. In some embodiments, the composition as described herein is negative for bacteria or fungi for at least 7 days in culture. [0380] In some embodiments, the composition as described herein is administered to the subject a plurality of times. In some embodiments, the composition as described herein is administered to the subject more than one time. In some embodiments, the composition as described herein is administered to the subject more than two times. In some embodiments, the composition as described herein is administered to the subject more than three times. In some embodiments, the composition as described herein is administered to the subject more than four times. In some embodiments, the composition as described herein is administered to the subject more than five times. In some embodiments, the composition as described herein is administered to the subject more than six times. In some embodiments, the composition as described herein is administered to the subject more than seven times. In some embodiments, the composition as described herein is administered to the subject more than eight times. In some embodiments, the composition as described herein is administered to the subject more than nine times. In some embodiments, the composition as described herein is administered to the subject more than ten times. In some embodiments, the composition as described herein is administered to the subject a number of times that are suitable for the subjects. In some embodiments, the composition is administered to the subject in periodic doses as provided herein, for the duration of the period that the subject is at high risk of a viral infection. In some embodiments, the composition is administered to the subject in periodic doses as provided herein, for the duration of the period that the subject is immunocompromised.

[0381] In some embodiments, the composition is administered to the subject weekly. In some embodiments, the composition is administered to the subject weekly for 4 weeks. In some embodiments, the composition is administered to the subject weekly for 5 weeks. In some embodiments, the composition is administered to the subject weekly for 6 weeks. In some embodiments, the composition is administered to the subject weekly for 7 weeks. In some embodiments, the composition is administered to the subject weekly for 8 weeks. In some embodiments, the composition is administered to the subject weekly for 9 weeks. In some embodiments, the composition is administered to the subject weekly for 10 weeks. In some embodiments, the composition is administered to the subject weekly for 11 weeks. In some embodiments, the composition is administered to the subject weekly for 12 weeks. In some embodiments, the composition is administered to the subject weekly for 13 weeks. In some embodiments, the composition is administered to the subject weekly for 14 weeks. In some embodiments, the composition is administered to a subject every two weeks. In some embodiments, the composition is administered to a subject every two weeks for 6 weeks. In some embodiments, the composition is administered to a subject every two weeks for 8 weeks. In some embodiments, the composition is administered to a subject every two weeks for 10 weeks. In some embodiments, the composition is administered to a subject every two weeks for 12 weeks. In some embodiments, the composition is administered to a subject every two weeks for 14 weeks. In some embodiments, the composition is administered to a subject every two weeks for 16 weeks. In some embodiments, the composition is administered to a subject every two weeks for 18 weeks. In some embodiments, the composition is administered to a subject every two weeks for 20 weeks. In some embodiments, the composition is administered to a subject every two weeks for 22 weeks. In some embodiments, the composition is administered to a subject every two weeks for 24 weeks. In some embodiments, the composition is administered to a subject every two weeks for 52 weeks. In some embodiments, the composition is administered every 14 days for 12 weeks. In some embodiments, the composition is administered every 14 days (± three days) for 12 weeks. In some embodiments, the composition is administered every 2 weeks for 14 weeks. In some embodiments, the composition is administered every 14 days for 14 weeks. In some embodiments, the composition is administered every 14 days (± three days) for 14 weeks. In some embodiments, the composition is administered every 2 weeks for 8 doses. In some embodiments, the composition is administered every 2 weeks for 7 doses. In some embodiments, the composition is administered in 7 doses wherein the doses are administered on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the composition is administered on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the composition is on day 1 and then every two weeks thereafter. In some embodiments, the composition is administered in 8 doses, wherein the doses are administered on day 1 and then every two weeks thereafter. In some embodiments, the composition is administered in 7 doses, wherein the doses are administered on day 1 and then every two weeks thereafter. In some embodiments, the doses are administered on day 1, day 15, day 29, day 43, day 57, day 71, and day 85. In some embodiments, the doses are administered on day 1 (± three days), day 15 (± three days), day 29 (± three days), day 43 (± three days), day 57 (± three days), day 71 (± three days), and day 85 (± three days). In some embodiments, the doses are administered on day 1, day 14, day 28, day 42, day 56, day 70, and day 84. In some embodiments, the doses are administered on day 1 (± three days), day 14 (± three days), day 28 (± three days), day 42 (± three days), day 56 (± three days), day 70 (± three days), and day 84 (± three days). In some embodiments, the composition comprises Posoleucel.

[0382] In some embodiments, the polyclonal population of VSTs is administered to a subject in a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject in a second treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject in a first and second treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject in a first and, optionally, a second treatment period.

[0383] In some embodiments, the composition is administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 ,14 ,15, 16 ,17, 18, 19 ,20, 21, 22, 23, 24, 25, 26 ,27, 28, 29, 30, 31, 32, 33, 34, or 35 days of the first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 4 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 5 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 6 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 7 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 8 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 9 days during a first treatment period. In some embodiments, the polyclonal population of VSTs is administered to a subject about every 10 days during a first treatment period.

[0384] In some embodiments, the first treatment period comprises administration of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 doses of the polyclonal population of VSTs. In some embodiments, the first treatment period comprises administration of one dose of the polyclonal population of VSTs. In some embodiments, the first treatment period comprises administration of two doses of the polyclonal population of VSTs. In some embodiments, the first treatment period comprises administration of three doses of the polyclonal population of VSTs. In some embodiments, the first treatment period comprises administration of four doses of the polyclonal population of VSTs.

[0385] In some embodiments, the first treatment period is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days. In some embodiments, the first treatment period is one week, two weeks, three weeks, four weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks long. In some embodiments, the first treatment period is continued until resolution of viremia or viral disease.

[0386] In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) weekly. In some embodiments, a subject is administered a composition described here (e.g., a compositions comprising a polyclonal population of VSTs) once a week for 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 2 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 3 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 4 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 5 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 6 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 7 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 8 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 9 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 10 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 11 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for 12 weeks. In some embodiments, a subject is administered a composition described here (e.g., a composition comprising a polyclonal population of VSTs) once a week for more than 12 weeks. In some embodiments, a subjected is administered a composition described herein once a week on a weekly basis until viral load is undetectable.

[0387] In some embodiments, the composition is administered at day zero, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15, day 16, day 17, day 18, day 19, day 20, day 21, or any combination thereof in the first treatment period.

[0388] In some embodiments, the composition is administered at day zero of the first treatment period. In some embodiments, the composition is administered at day 7 of the first treatment period. In some embodiments, the composition is administered at about day 7 of the first treatment period. In some embodiments, the composition is administered at day 14 of the first treatment period. In some embodiments, the composition is administered at about day 14 of the first treatment period. In some embodiments, the composition is administered at day 0, day 7, and day 14 of the first treatment period. In some embodiments, the composition is administered at day 0, about day 7, and about day 14 of the first treatment period.

[0389] In some embodiments, the composition is administered to a subject every 7 days for 2 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 2 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days for 3 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 3 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days for 4 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 4 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days for 5 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 5 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days for 6 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 6 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days for 7 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 7 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days for 8 weeks of the first treatment period. In some embodiments, the composition is administered to a subject every 7 days (± three days) for 8 weeks of the first treatment period.

[0390] In some embodiments, the composition is administered every 7 days for 1 week of the first treatment period. In some embodiments, the composition is administered every 7 days for 2 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 3 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 4 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 5 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 6 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 7 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 8 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 9 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 10 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 11 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 12 weeks of the first treatment period. [0391] In some embodiments, the composition is administered every 7 days (± three days) for 1 week of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 2 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days for 3 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 4 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 5 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 6 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days(± three days) for 7 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 8 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 9 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 10 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 11 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days) for 12 weeks of the first treatment period. In some embodiments, the composition is administered every 7 days (± three days).

[0392] In some embodiments, the second treatment period comprises administration of one dose of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of two doses of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of three doses of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of four doses of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of five doses of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of six doses of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of seven doses of the polyclonal population of VSTs. In some embodiments, the second treatment period comprises administration of eight doses of the polyclonal population of VSTs.

[0393] In some embodiments, the composition is administered to a subject every 14 days for 6 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days (± three days) for 6 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days for

7 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days (± three days) for 7 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days for

8 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days (± three days) for 8 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days for

9 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days (± three days) for 9 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days for

10 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 14 days (± three days) for 10 weeks of the second treatment period.

[0394] In some embodiments, the composition is administered to a subject every 28 days for

6 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days (± three days) for 6 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days for

7 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days (± three days) for 7 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days for

8 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days (± three days) for 8 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days for

9 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days (± three days) for 9 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days for

10 weeks of the second treatment period. In some embodiments, the composition is administered to a subject every 28 days (± three days) for 10 weeks of the second treatment period.

[0395] In some embodiments, the composition is administered every 14 days for 1 week of the second treatment period. In some embodiments, the composition is administered every 14 days for 2 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 3 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 4 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 5 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 6 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 14 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 8 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 9 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 10 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 11 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 12 weeks of the second treatment period.

[0396] In some embodiments, the composition is administered every 14 days (± three days) for 1 week of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 2 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 3 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 4 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 5 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 6 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days(± three days) for 7 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 8 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 9 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 10 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 11 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 12 weeks of the second treatment period.

[0397] In some embodiments, the composition is administered every 14 days for 1 week of the second treatment period. In some embodiments, the composition is administered every 14 days for 2 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 3 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 4 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 5 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 6 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 14 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 8 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 9 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 10 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 11 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 12 weeks of the second treatment period.

[0398] In some embodiments, the composition is administered every 14 days (± three days) for 2 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 3 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 4 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 5 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 6 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days(± three days) for 7 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 8 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 9 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 10 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 11 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days (± three days) for 12 weeks of the second treatment period.

[0399] In some embodiments, the composition is administered every 14 days for 1 week of the second treatment period. In some embodiments, the composition is administered every 14 days for 2 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 3 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 4 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 5 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 6 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 14 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 8 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 9 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 10 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 11 weeks of the second treatment period. In some embodiments, the composition is administered every 14 days for 12 weeks of the second treatment period.

[0400] In some embodiments, the composition is administered every 28 days (± three days) for 4 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 5 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 6 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days(± three days) for 7 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 8 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 9 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 10 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 11 weeks of the second treatment period. In some embodiments, the composition is administered every 28 days (± three days) for 12 weeks of the second treatment period.

[0401] In some embodiments, the first and second treatment period together are about 8 weeks long. In some embodiments, the first and second treatment period together are about 9 weeks long. In some embodiments, the first and second treatment period together are about 10 weeks long. In some embodiments, the first and second treatment period together are about 11 weeks long. In some embodiments, the first and second treatment period together are about 12 weeks long. In some embodiments, the first and second treatment period together are about 13 weeks long. In some embodiments, the first and second treatment period together are about 14 weeks long. In some embodiments, the first and second treatment period together are about 15 weeks long.

[0402] In some embodiments, a composition described herein is administered to a subject every seven days for three weeks, followed by administration to the subject every 14 days. In some embodiments, a composition described herein is administered to a subject every 7 days for three weeks, followed by administration to the subject every 28days.

[0403] In some embodiments, a composition described herein is administered to a subject every seven days for three weeks, followed by administration to the subject every 14 days. In some embodiments, a composition described herein is administered to a subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days).

[0404] In some embodiments, a composition described herein is administered to a subject every seven days for three weeks, followed by administration to the subject every 28 days. In some embodiments, a composition described herein is administered to a subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days).

[0405] Re-Dosing

[0406] In some embodiments, a subject is re-dosed with the compositions described herein. In some embodiments, a subject is re-dosed with a composition described herein if they did not respond to the initial dose. In some embodiments, a subject is re-dosed with a composition described herein if they experienced a less than 1 log decrease in viral load as compared to baseline. In some embodiments, a subject is re-dosed with a composition described herein if they did not experience a durable decrease in viral load. In some embodiments, a subject is re-dosed with a composition described herein if they experienced an increase in viral load after an initial response.

[0407] In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is re-dosed after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that did not respond to an initial dose is re-dosed after the primary endpoint of the initial treatment regimen. In some embidiments, a subject that did not experience a durable decrease in viral load is re-dosed after the primary endpoint of the initial treatment regimen.

[0408] In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is re-dosed at week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, or more. In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is re-dosed at 1 year. In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is redosed at about 2 months to about 12 months. In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is re-dosed at about 2 weeks to about 12 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is re-dosed at about 2 weeks to about 6 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that experienced a less than 1 log decrease in viral load as compared to baseline is re-dosed at about 2 weeks to about 2 months after the primary endpoint of the initial treatment regimen.

[0409] In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed at week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, or more.. In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed at 1 year. In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed at about 2 months to about 12 months. In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed at about 2 weeks to about 12 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed at about 2 weeks to about 6 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that experienced an increase in viral load after an initial response is re-dosed at about 2 weeks to about 2 months after the primary endpoint of the initial treatment regimen.

[0410] In some embodiments, a subject that did not respond to an initial dose is re-dosed at week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, or more.. In some embodiments, a subject that did not respond to an initial dose is re-dosed at 1 year. In some embodiments, a subject that did not respond to an initial dose is re-dosed at about 2 months to about 12 months. In some embodiments, a subject that did not respond to an initial dose is redosed at about 2 weeks to about 12 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that did not respond to an initial dose is re-dosed at about 2 weeks to about 6 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that did not respond to an initial dose is re-dosed at about 2 weeks to about 2 months after the primary endpoint of the initial treatment regimen.

[0411] In some embodiments, a subject that did not experience a durable decrease in viral load is re-dosed at week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, or more. In some embodiments, a subject that did not experience a durable decrease in viral load is redosed at 1 year. In some embodiments, a subject that did not experience a durable decrease in viral load is re-dosed at about 2 months to about 1 year. In some embodiments, a subject that did not experience a durable decrease in viral load is re-dosed at about 2 weeks to about 12 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that did not experience a durable decrease in viral load is re-dosed at about 2 weeks to about 6 months after the primary endpoint of the initial treatment regimen. In some embodiments, a subject that did not experience a durable decrease in viral load is re-dosed at about 2 weeks to about 2 months after the primary endpoint of the initial treatment regimen. [0412] In some embodiments, the subject is re-dosed with the same VST cell line as administered during the initial dosing regimen. In some embodiments, the subject is re-dosed with a different VST cell line.

[0413] In some embodiments, a subject is administered two or more compositions described herein. In some embodiments, a subject is administered two or more VST cell lines described herein. In some embodiments, a subject is administered three or more VST cell lines described herein. In some embodiments, a subject is administered two or more compositions described herein if they experienced a less than 1 log decrease in viral load as compared to baseline. In some embodiments, a subject is administered two or more VST cell lines described herein if they experienced a less than 1 log decrease in viral load as compared to baseline. In some embodiments, a subject is administered three or more VST cell lines described herein if they experienced a less than 1 log decrease in viral load as compared to baseline. In some embodiments, the two or more VST cell lines have the same number of matching HLA alleles to the solid organ transplant. In some embodiments, the two or more VST cell lines have the same number of matching HLA alleles to the patient. In some embodiments, the two or more VST cell lines have a different number of matching HLA alleles to the solid organ transplant. In some embodiments, the two or more VST cell lines have a different number of matching HLA alleles to the patient. [0414] In some embodiments, the two or more VST cell lines have different HLA matching to the solid organ transplant. In some embodiments, the two or more VST cell lines have the same HLA matching to the solid organ transplant. In some embodiments, the two or more VST cell lines have different HLA matching to the patient. In some embodiments, the two or more VST cell lines have the same HLA matching to the patient.

[0415] In some embodiments, a second VST cell line is administered to a subject when a viral infection persists after administration of a first VST cell line. In some embodiments, a second VST cell line is administered to a subject after reactivation of a virus. In some embodiments, a second VST cell line is administered to a subject if the subject expereiemces a less than 1 log decrease in viral load after administration of a first VST cell line.

[0416] In some embodiments, a subject is administered a first VST composition described herein to treat or prevent a viral infection and is subsequently administered a second VST composition described herein.

[0417] In some embodiments, a subject is administered two VST cell lines wherein the cell lines are administered concurrently. In some embodiments, a subject is administered two VST cell lines wherein the cell lines are administered at least 1 week apart, at least two weeks apart, at least three weeks apart, at least one month apart, at least two months apart, at least three months apart, at least four months apart, at least five months apart, at least 6 months apart, at least 7 months apart, at least 8 months apart, at least 9 months apart, at least 10 months apart, at least 11 months apart, at least 1 year apart, at least 2 years apart, at least 3 years apart, or at least 4 years apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least one month apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least two months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least three months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least four months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least five months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least six months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least seven months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least eight months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least nine months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least ten months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least eleven months apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least 1 year apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least two years apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least three years apart. In some embodiments, a subject is administered two VST cells lines wherein the cell lines are administered at least 4 years apart.

Methods of Treatment

[0418] In some embodiments, the method of treatment is associated with an acceptable safety profile. In some embodiments, the safety profile is determined by assessing one or more of treatment-emergent adverse events, changes in vital signs, physical examination, hematology blood tests, clinical chemistry blood tests, urinalysis, and electrocardiogram (ECG). In some embodiments, the safety profile is determined by assessing treatment-emergent adverse events. In some embodiments, the safety profile is determined by assessing changes in vital signs. In some embodiments, the safety profile is determined by assessing changes in physical examination. In some embodiments, the safety profile is determined by assessing changes in hematology blood tests. In some embodiments, the safety profile is determined by assessing changes in clinical chemistry blood tests. In some embodiments, the safety profile is determined by assessing changes in urinalysis. In some embodiments, the safety profile is determined by assessing changes in electrocardiogram (ECG). A person of skill in the art is able to assess the safety profile of a subject to determine if any one or more of treatment- emergent adverse events, changes in vital signs, physical examination, hematology blood tests, clinical chemistry blood tests, urinalysis, and electrocardiogram (ECG) fall outside of a normal or safe range for a subj ect.

[0419] In some embodiments, the subject is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the subject is the recipient of a kidney transplant and an additional solid organ transplant. In some embodiments, the subject is the recipient of a kidney transplant and one or more additional solid organ transplants. In some embodiments, the one or more additional solid organ transplants are selected from a heart transplant and/or a pancreas transplant. In some embodiments, the additional solid organ transplant is a heart transplant. In some embodiments, the additional solid organ transplant is a pancreas transplant. In some embodiments, the subject is the recipient of a kidney transplant and a heart transplant. In some embodiments, the subject is the recipient of a kidney transplant and a pancreas transplant.

[0420] In some embodiments, the method comprises monitoring blood and/or urine of the subject for BK virus, CMV, AdV, EBV, JCV, and/or HHV-6.In some embodiments, the method comprises monitoring blood and/or urine of the subject for BK virus, CMV, AdV, EBV, JCV, and/or HHV-6 using PCR assays. In some embodiments, the method comprises monitoring blood and/or urine of the subject for BK virus. In some embodiments, the method comprises monitoring blood and/or urine of the subject for BK virus using PCR assays. [0421] In some embodiments, the method comprises monitoring blood of the subject for BK virus, CMV, AdV, EBV, JCV, and/or HHV-6. In some embodiments, the method comprises monitoring blood of the subject for BK virus, CMV, AdV, EBV, JCV, and/or HHV-6 using PCR assays. In some embodiments, the method comprises monitoring blood of the subject for BK virus. In some embodiments, the method comprises monitoring blood of the subject for BK virus using PCR assays.

[0422] In some embodiments, the method comprises monitoring urine of the subject for BK virus, CMV, AdV, EBV, JCV, and/or HHV-6. In some embodiments, the method comprises monitoring urine of the subject for BK virus, CMV, AdV, EBV, JCV, and/or HHV-6 using PCR assays. In some embodiments, the method comprises monitoring urine of the subject for BK virus. In some embodiments, the method comprises monitoring urine of the subject for BK virus using PCR assays.

[0423] In some embodiments, the method results in an improvement of a subjects estimated glomerular filtration rate (eGFR) compared to the eGFR of the subject prior to administration of a composition described herein, and/or compared to the eGFR of a subject who received a placebo treatment. In some embodiments, the method results in an improvement of a subjects estimated glomerular filtration rate (eGFR) compared to the eGFR of the subject prior to administration of a composition comprising a polyclonal population of VSTs described herein. In some embodiments, the method results in an improvement of a subjects estimated glomerular filtration rate (eGFR) compared to the eGFR of a subject who received a placebo treatment.

[0424] In some embodiments, the method results in an improvement of a subjects eGFR wherein the improvement is an increase in eGFR of about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or more compared to the eGFR of the subject prior to administration of the composition and/or compared to the eGFR of a subject who received a placebo treatment. In some embodiments, the method results in an improvement of a subjects eGFR wherein the improvement is an increase in eGFR of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the eGFR of the subject prior to administration of the composition and/or compared to the eGFR of a subject who received a placebo treatment. In some embodiments, the results in an improvement of a subjects estimated eGFR wherein the improvement is an increase in eGFR of about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or more compared to the eGFR of the subject prior to administration of a composition comprising a polyclonal population of VSTs described herein. In some embodiments, the method results in an improvement of a subjects estimated eGFR wherein the improvement is an increase in eGFR of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the eGFR of the subject prior to administration of a composition comprising a polyclonal population of VSTs described herein. In some embodiments, the results in an improvement of a subjects eGFR wherein the improvement is an increase in eGFR of about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or more compared to the eGFR of a subject who received a placebo treatment.

[0425] In some embodiments, the results in an improvement of a subjects eGFR wherein the improvement is an increase in eGFR of about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the eGFR of a subject who received a placebo treatment.

[0426] In some embodiments, the method prevents a decline in a subjects estimated glomerular filtration rate (eGFR) compared to the eGFR of a subject who received a placebo treatment. In some embodiments, the method the method prevents a decline in a subjects estimated glomerular filtration rate (eGFR). In some embodiments, the method prevents a large decline in a subjects estimated glomerular filtration rate (eGFR) compared to the eGFR of a subject who received a placebo treatment. In some embodiments, the method the method prevents a large decline in a subjects estimated glomerular filtration rate (eGFR). In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR). In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 10% to about 60% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 20% to about 70% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 10% to about 60%. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 20% to about 70%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 30% to about 60% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 30% to about 60%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 40% to about 60% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 40% to about 60%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 50% to about 60% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 50% to about 60%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 55% to about 60% compared to the eGFR decline of a subject who received a placebo treatment In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 55% to about 60%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 50% to about 70% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 50% to about 70%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 20% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 20%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 30% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 30%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 40% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 40%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 50% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 50%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 57% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 57%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 60% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 60%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 70% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 70%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 80% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 80%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 90% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 90%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 95% compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 95%. In some embodiments, the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 99% or more compared to the eGFR decline of a subject who received a placebo treatment. In some embodiments, the method the method reduces the decline in a subjects estimated glomerular filtration rate (eGFR) by about 99% or more.

[0427] In some embodiments, the method reduces the decline in a subjects eGFR by greater than 2.5 mL/min/1.73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subjects eGFR by greater than 2.5 mL/min/1.73mm ² per year. In some embodiments, the method reduces the decline in a subjects eGFR by about 2.5 mL/min/1.73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subjects eGFR by about 2.5 mL/min/1.73mm ² per year. In some embodiments, the method reduces the decline in a subject eGFR by about 5 mL/min/1 ,73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subject eGFR by about 5 mL/min/1.73mm ² . In some embodiments, the method reduces the decline in a subject eGFR by about 10 mL/min/1 ,73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subject eGFR by about 10 mL/min/1.73mm ² per year. In some embodiments, the method reduces the decline in a subjects eGFR by greater than 10 mL/min/1.73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subject eGFR by greater than 10 mL/min/1.73mm ² per year. In some embodiments, the method reduces the decline in a subjects eGFR by about 2.5 mL/min/1.73mm ² per year to about 10 mL/min/1.73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subjects eGFR by about 2.5 mL/min/1.73mm ² per year to about 10 mL/min/1.73mm ² per year per year. In some embodiments, the method reduces the decline in a subjects eGFR by about 2.5 mL/min/1.73mm ² per year to about 5 mL/min/1.73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subjects eGFR by about 2.5 mL/min/1 ,73mm ² per year to about 5 mL/min/1 ,73mm ² per year per year. In some embodiments, the method reduces the decline in a subjects eGFR by about 5 mL/min/1 ,73mm ² per year to about 10 mL/min/1 ,73mm ² per year compared to a subject who received placebo treatment. In some embodiments, the method reduces the decline in a subjects eGFR by about 5 mL/min/1.73mm ² per year to about 10 mL/min/1.73mm ² per year per year.

[0428] In some embodiments, the method reduces the decline in a subjects eGFR and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR and the subject has a viral load decrease of 1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load.

[0429] In some embodiments, the method reduces the decline in a subjects eGFR as compared to a subject administered placebo and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR as compared to a subject administered placebo and the subject has a viral load decrease of 1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR as compared to a subject administered placebo and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load.

[0430] In some embodiments, the method reduces the decline in a subjects eGFR by at least 10% and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR by at least 10% and the subject has a viral load decrease of 1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR by at least 10% and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR by about 10% to about 70% and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR by about 10% to about 70% and the subject has a viral load decrease of 1 logio copies/mL relative to baseline BK viral load. In some embodiments, the method reduces the decline in a subjects eGFR by about 10% to about 70% and the subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load.

[0431] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein has an undetectable level of urinary polyomavirus haufen. In some embodiments, a subject has undetectable levels of urinary polyomavirus haufen prior to treatment (e.g., with a composition comprising a polyclonal population of VSTs). In some embodiments, a subject has undetectable levels of urinary polyomavirus haufen during treatment. In some embodiments, a subject has undetectable levels of urinary polyomavirus haufen for 12 weeks following treatment.

[0432] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein has improved glomerular filtration rate (eGFR) compared to eGFR of the subject prior to administration of the composition. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein has improved eGFR compared to the serum eGFR of a subject who receives a placebo treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein maintains a stable eGFR. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described does not have a large decline in eGFR. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described does not have a decline in eGFR.

[0433] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein has improved serum creatine levels compared to serum creatine levels of the subject prior to administration of the composition. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein has improved serum creatine levels compared to the serum creatine levels of a subject who receives a placebo treatment.

[0434] In some embodiments, the disclosure provides a method which results in an improvement in a subject’s serum creatine levels compared to the serum creatine levels of the subject prior to administration of a composition described herein, and/or compared to the serum creatine levels of a subject who received a placebo treatment.

[0435] In some embodiments, a subject is administered a composition comprising a polyclonal population of VSTs described herein, wherein administration increases serum creatine levels about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the serum creatine levels of the subject prior to administration of the composition. In some embodiments, a subject is administered a composition comprising a polyclonal population of VSTs described herein, wherein administration increases serum creatine levels about 10%, about 25%, about 50%, about 75%, about 90%, or more compared to the serum creatine levels of a subject who receives a placebo treatment.

In some embodiments, the method results in an improved iBox score. The iBox scoring system is a biomarker panel used post-transplant in patients which includes one or more of the variables selected from time from transplant, eGFR, proteinuria, donor specific antibodies (DSA), and histological features to predict graft failure and is a method known to those of skill in the art. In some embodiments, the iBox score is measured using the methods described in U.S. Publication No. US20220293274. In some embodiments, proteinuria is measured in a subject described herein. In some embodiments, the levels of protein in the urine are reduced. In some embodiments, the levels of protein in the urine of a subject are reduced after administration of a composition comprising a polyclonal population of VSTs described herein. In some embodiments, a subject administered a polyclonal population of VSTs described herein has a lower rate of increased urine/protein creatine ratio as compared to a subject administered placebo. In some embodiments, a subject administered a polyclonal population of VSTs described herein has a lower rate of increased urine/protein creatine ratio as compared to baseline. In some embodiments, a subject administered a polyclonal population of VSTs described herein has a lower rate of increased urine/protein creatine ratio as compared to placebo. In some embodiments, a subject administered a polyclonal population of VSTs described herein has a lower rate of increased urine/protein creatine ratio. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 25%. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 25% as compared to baseline. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 25% as compared to placebo. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 50%. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 50% as compared to baseline. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 50% as compared to placebo. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 1g per day. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 1g per day as compared to baseline. In some embodiments, the rate of increase of the urine/protein creatine ratio is reduced by at least 1g per day as compared to placebo.

[0436] In some embodiments, a subjects urine/protein creatinine ratio is reduced by at least 50% as compared to a subject administered placebo. In some embodiments, a subjects urine/protein creatinine ratio is reduced by at least 50%. In some embodiments, a subjects estimated 24 hour proteinuria is reduced by at least 50% as compared to a subject administered placebo. In some embodiments, a subjects estimated 24 hour proteinuria is reduced by at least 50%. In some embodiments, a subjects urine/protein creatinine ratio is reduced to about less than 1 g per day as compared to a subject administered placebo. In some embodiments, a subjects urine/protein creatinine ratio is reduced to about less than 1 g per day. In some embodiments, a subjects estimated 24 hour proteinuria is reduced to about less than 1 g per day as compared to a subject administered placebo. In some embodiments, a subjects estimated 24 hour proteinuria is reduced to about less than 1 g per day. In some embodiments, a subjects urine/protein creatinine ratio or is reduced to about less than 500 mg per day as compared to a subject administered placebo. In some embodiments, a subjects urine/protein creatinine ratio or is reduced to about less than 500 mg per day. In some embodiments, a subjects estimated 24 hour proteinuria is reduced to about less than 500 mg per day as compared to a subject administered placebo. In some embodiments, a subjects estimated 24 hour proteinuria is reduced to about less than 500 mg per day. In some embodiments, a subject urine/protein creatinine ratio is reduced by 50% or more relative to the subjects baseline ratio. In some embodiments, a subject urine/protein creatinine ratio is reduced by 25% or more relative to the subjects baseline ratio. In some embodiments, the method results in improved grading of BK virus associated nephropathy (BKVAN) via histological analysis of a biopsy of transplanted tissue. Grading of BKVAN biopsy samples is a method known to those of skill in the art. In some embodiments, the histologic patterns of a BKVAN biopsy are characterized using the American Society of Transplantation-Infectious Disease Community of Practice methods (Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4: 179-88). In some embodiments, the histologic patterns of a BKVAN biopsy are characterized using the Banff 2017 Working Group Classification (Nickel eit V, et al. The Banff Working Group classification of definitive polyomavirus nephropathy: morphologic definitions and clinical correlations. J Am Soc Nephrol 2018;29:680-93). [0437] In some embodiments, a subject is administered a composition comprising a polyclonal population of VSTs described herein to treat BK virus-associated nephropathy. In some embodiments, the disclosure provides a method for treating or preventing BK virus- associated nephropathy in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) described herein. In some embodiments, the disclosure provides a method of treating or preventing BK virus-associated nephropathy (BKVAN). In some embodiments, the disclosure provides a method for treating or preventing BK virus- associated nephropathy in a subject in need thereof, wherein the subject is the recipient of a solid organ transplant, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) described herein. [0438] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome during treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome for at least 2 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome for at least 4 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome for at least 6 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome for at least 8 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome for at least 10 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience cytokine release syndrome for at least 12 weeks after treatment. In some embodiments, the rate of cytokine release syndrome after administering a composition comprising a polyclonal population of VSTs described herein to a population of subjects is less than about 20% in the population of subjects, less than about 15% in the population of subjects, less than about 10% in the population of subjects, less than about 9% in the population of subjects, less than about 8% in the population of subjects, less than about 7% in the population of subjects, less than about 6% in the population of subjects, less than about 5% in the population of subjects, less than about 4% in the population of subjects, less than about 3% in the population of subjects, less than about 2% in the population of subjects, or less than about 1% in the population of subjects.

[0439] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience a severe adverse event (SAE). In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an adverse event. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an adverse event > Grade 1. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an adverse event > Grade 2. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an adverse event > Grade 3. The presence of an adverse event in a patient is known by those of skill in the art. For example, adverse events and toxicities are graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE).

[0440] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection during treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection for at least 2 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection for at least 4 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection for at least 6 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection for at least 8 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection for at least 10 weeks after treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of acute rejection for at least 12 weeks after treatment.

[0441] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein does not experience an episode of graft versus host disease. In some embodiments, if a subject administered a composition comprising a polyclonal population of VSTs described herein experiences an episode of GVHD, the stage of GVHD is stage 2 or lower. In some embodiments, if a subject administered a composition comprising a polyclonal population of VSTs described herein experiences an episode of GVHD, the stage of GVHD is stage 1 or lower. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 2 GVHD during treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 2 GVHD for 12 weeks following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 1 GVHD during treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease (GVHD) greater than or equal to stage 1 GVHD for 12 weeks following treatment.

[0442] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease prior to treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease during treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not experience an episode of graft versus host disease 12 weeks following treatment.

[0443] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and does not experience graft rejection. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for one to five years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for two to five years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for one to three years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for one to two years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for three to five years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for four to five years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for one to ten years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for five to ten years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for more than five years following treatment compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and has a reduced risk for graft rejection for more than ten years following treatment compared to a subject administered placebo.

[0444] In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss for about 1 year to about 5 years following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss for about 1 year to about 10 years following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss for 1 year or greater following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss for 5 years or greater following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss for 10 years or greater following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss 1 year following the solid organ transplantation compared to a population of

I l l subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss 2 years following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss 3 years following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss 4 years following the solid organ transplantation compared to a population of subjects administered placebo. In some embodiments, a population of subjects administered a composition comprising a polyclonal population of VSTs described herein and who have received a solid organ transplant (SOT) have at least a 10%, at least a 20%, at least a 30%, at least a 40%, at least a 50%, at least a 60%, at least a 70%, at least an 80%, or at least a 90% reduced rate of allograft loss 5 years following the solid organ transplantation compared to a population of subjects administered placebo.

[0445] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences prolonged transplant survival. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences prolonged transplant survival as compared to a subject administered placebo. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences lifelong transplant survival. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to two years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to three years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for two to five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for three to five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for four to five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to ten years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for five to ten years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for more than five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for more than ten years following treatment.

[0446] In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences prolonged transplant survival. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences prolonged transplant survival as compared to a viremic subject administered placebo. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences lifelong transplant survival. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to five years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to two years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to three years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for two to five years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for three to five years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for four to five years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for one to ten years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for five to ten years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for more than five years following treatment. In some embodiments, a viremic subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for more than ten years following treatment.

[0447] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival one year following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least one year following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival two years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least two years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival three years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least three years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival four years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least four years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least five years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival six years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least six years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival seven years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least seven years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival eight years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least eight years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival nine years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least nine years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival ten years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival for at least ten years following treatment. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs described herein is a recipient of a solid organ transplant (SOT) and experiences transplant survival ten or more years following treatment. In some embodiments, the solid organ transplant is a kidney transplant. In some embodiments, the subject is a verimic subject.

[0448] In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not develop de novo antibodies directed against HL A molecules present on the VSTs. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not develop de novo antibodies directed against shared HLA molecules present on the VSTs and the transplanted organ. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not develop de novo antibodies directed against HLA molecules present on the transplanted organ. In some embodiments, a subject administered a composition comprising a polyclonal population of VSTs does not develop one or more of i) anti-HLA antibodies directed to alleles exclusively present on the VSTs; ii) anti -HL A antibodies directed to alleles shared by the infused VSTs and the allograft iii) anti-HLA antibodies directed to alleles exclusively present on the allograft. . [0449] In some embodiments, a subject does not have liver dysfunction. In some embodiments, a subject does not have liver dysfunction prior to administration of a composition described herein. In some embodiments, a subject does not have liver dysfunction during treatment of a composition described herein. In some embodiments, a subject does not have liver dysfunction following administration of a composition described herein. In some embodiments, a subject does not have liver dysfunction for 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, or 14 weeks following administration of a composition described herein. In some embodiments, a subject does not have liver dysfunction for 12 weeks following administration of a composition described herein. [0450] Examples of liver dysfunction include, but is not limited to, inherited liver diseases, fatty liver disease, liver cirrhosis, non-alcoholic fatty liver disease, liver cancer, hemochromatosis, and hepatitis. In some embodiments, liver dysfunction is transaminase more than 5 times the upper limit of normal (ULN) reference transaminase levels. In some embodiments, liver dysfunction is direct bilirubin levels more than two times the ULN reference bilirubin levels. In some embodiments, liver dysfunction is transaminase more than 5 times the upper limit of normal (ULN) reference transaminase level and/or direct bilirubin levels more than two times the ULN reference. In some embodiments, liver dysfunction is transaminase more than 5 times the upper limit of normal (ULN) reference transaminase level and/or total bilirubin levels more than two times the ULN reference.

[0451] In some embodiments, a subject does not have renal dysfunction. In some embodiments, a subject does not have renal dysfunction prior to administration of a composition described herein. In some embodiments, a subject does not have renal dysfunction during administration of a composition described herein. In some embodiments, a subject does not have renal dysfunction following administration of a composition described herein. In some embodiments, a subject does not have renal dysfunction for 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, or 14 weeks following administration of a composition described herein. In some embodiments, a subject does not have renal dysfunction for 12 weeks following administration of a composition described herein. [0452] In some embodiments, renal dysfunction is defined by an estimated glomerular filtration rate (eGFR) of < 90 mL/min/1.73m ² . In some embodiments, renal dysfunction is defined by an estimated glomerular filtration rate (eGFR) of < 20 mL/min/1.73m ² . In some embodiments, renal dysfunction is defined by an estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m ² . In some embodiments, increased eGFR demonstrates improved renal function. In some embodiments, decreased eGFR demonstrated increased renal dysfunction. In some embodiments, the method results in reduction of BK viral load in a subject compared to BK viral load in the subject prior to administration of a composition described herein (e.g. a composition comprising a polyclonal population of VSTs).

[0453] In some embodiments, a subject’s blood sample is subjected to TCRvP sequencing to measure the presence of Posoleucel cells in the blood sample. In some embodiments, TCRs unique to Posoleucel are detected in a blood sample. In some embodiments, Posoleucel VSTs are measured in a blood sample by TCRvP sequencing. In some embodiments, TCRs unique to Posoleucel are detected in a patient blood sample after treatment but are not present in the patient sample at baseline. In some embodiments, Posoleucel VSTs are measured in a blood sample by TCRvP sequencing at week 4 of treatment. In some embodiments, Posoleucel VSTs are measured in a blood sample by TCRvP sequencing at week 12 of treatment. In some embodiments, Posoleucel VSTs are measured in a blood sample by TCRvP sequencing at week 24 of treatment. In some embodiments, Posoleucel VSTs are measured in a blood sample by TCRvP sequencing 12 weeks after the final infusion of treatment.

[0454] In some embodiments, a subject’s blood sample is subjected to TCRvP sequencing to measure the presence of BK-specific T cells in the blood sample. In some embodiments, TCRs unique to BK-specific T cells are detected in a blood sample. In some embodiments, BK-specific T cells are measured in a blood sample by TCRvP sequencing. In some embodiments, TCRs unique to BK-specific T cells are detected in a patient blood sample after treatment but are not present in the patient sample at baseline. In some embodiments, BK-specific T cells are measured in a blood sample by TCRvP sequencing at week 4 of treatment. In some embodiments, BK-specific T cells are measured in a blood sample by TCRvP sequencing at week 12 of treatment. In some embodiments, BK-specific T cells are measured in a blood sample by TCRvP sequencing at week 24 of treatment. In some embodiments, BK-specific T cells are measured in a blood sample by TCRvP sequencing 12 weeks after the final infusion of treatment. [0455] In some embodiments, the BK viral load in a subject is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, the BK viral load in a subject is reduced by about 10%, about 25%, about 50%, about 75%, about 90%, or more relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 10% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 20% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 30% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 40% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 50% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 60% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 70% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 80% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 90% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 95% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the BK viral load in a subject is reduced by about 99% relative to BK viral load prior to administration of a composition described herein. In some embodiments, the composition comprises Posoleucel.

[0456] In some embodiments, the methods described herein result in a stable viral load for about 12 weeks to about 24 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 12 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 13 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 14 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 15 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 16 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 17 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 18 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 19 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 20 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 21 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 22 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 23 weeks in a subject. In some embodiments, the methods described herein result in a stable viral load for at least 24 weeks in a subject.

[0457] In some embodiments, the BK viral load in a subject is reduced compared to BK viral load in a subject prior to administration of a composition described herein. In some embodiments, one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced compared to one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject prior to administration of a composition described herein. In some embodiments, the method results in a mean loglO change in viral load of about -0.5 from baseline. In some embodiments, the method results in a mean log 10 change in viral load of about -0.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a mean log 10 change in viral load of about -1.0 from baseline. In some embodiments, the method results in a mean loglO change in viral load of about -1.0 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a mean loglO change in viral load of about -1.5 from baseline. In some embodiments, the method results in a mean loglO change in viral load of about -1.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -0.25 from baseline. In some embodiments, the method results in a median loglO change in viral load of about -0.25 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -0.5 from baseline. In some embodiments, the method results in a median loglO change in viral load of about -0.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -1.0 from baseline. In some embodiments, the method results in a median log 10 change in viral load of about -1.0 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a median log 10 change in viral load of about -1.5 from baseline. In some embodiments, the method results in a median loglO change in viral load of about -1.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein.

[0458] In some embodiments, the method results in a loglO change in viral load of about -0.5 from baseline. In some embodiments, the method results in a loglO change in viral load of about -0.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a loglO change in viral load of about -1.0 from baseline. In some embodiments, the method results in a loglO change in viral load of about -1.0 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a loglO change in viral load of about -1.5 from baseline. In some embodiments, the method results in a loglO change in viral load of about -1.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a loglO change in viral load of about -0.25 from baseline. In some embodiments, the method results in a loglO change in viral load of about -0.25 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a loglO change in viral load of about -0.5 from baseline. In some embodiments, the method results in a loglO change in viral load of about - 0.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a loglO change in viral load of about -1.0 from baseline. In some embodiments, the method results in a loglO change in viral load of about -1.0 from baseline, wherein baseline is viral load prior to administration of a composition described herein. In some embodiments, the method results in a loglO change in viral load of about -1.5 from baseline. In some embodiments, the method results in a loglO change in viral load of about -1.5 from baseline, wherein baseline is viral load prior to administration of a composition described herein.

[0459] In some embodiments, the method results in a reduction of BK viral load in a subject compared to BK viral load of a subject who received a placebo treatment. In some embodiments, placebo treatment is cryopreservation media without cells. In some embodiments, placebo treatment is administered in the same volume as the treatment. In some embodiments, the BK viral load in a subject is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by about 10%, about 25%, about 50%, about 75%, about 90%, or more relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 10% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 20% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 30% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 40% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 50% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 60% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 70% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 80% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 90% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 95% relative to BK viral load of a subject who received a placebo treatment. In some embodiments, the BK viral load in a subject is reduced by at least 99% relative to BK viral load of a subject who received a placebo treatment.

[0460] In some embodiments, viral load of a subject with a high-grade baseline viral load (>5,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline viral load. In some embodiments, BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject with a high-grade baseline BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load (>5,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load. In some embodiments, BKV viral load of a subject with a high-grade baseline BKV viral load (>5,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline BKV viral load. In some embodiments, BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject with a high-grade baseline BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load (>5,000 copies/mL) is reduced by one or more logs. In some embodiments, BKV viral load of a subject with a high-grade baseline BKV viral load (>5,000 copies/mL) is reduced by one or more logs. In some embodiments, BKV viral load of a subject with a high-grade baseline BKV viral load (>10,000 copies/mL) is reduced by one or more logs.

[0461] In some embodiments, viral load of a subject with a high-grade baseline viral load (>10,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline viral load. In some embodiments, BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject with a high-grade baseline BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load (>10,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load. In some embodiments, BKV viral load of a subject with a high-grade baseline BKV viral load (>10,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline BKV viral load. In some embodiments, BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject with a high-grade baseline BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load (>10,000 copies/mL) is reduced by one or more logs. In some embodiments, BKV viral load of a subject with a high-grade baseline BKV viral load (>10,000 copies/mL) is reduced by one or more logs.

[0462] In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 10% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 20% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 30% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 40% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 50% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 60% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 70% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 80% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 90% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 95% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by at least 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>5,000 copies/mL) is reduced by one or more logs.

[0463] In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 10% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 20% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 30% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 40% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 50% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 60% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 70% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 80% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 90% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 95% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by at least 99% relative to the subject’s baseline BK viral load. In some embodiments, BK viral load of a subject with a high-grade baseline BK viral load (>10,000 copies/mL) is reduced by one or more logs. [0464] In some embodiments, a subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load (i.e., a 90% reduction in viral load and/or the viral load is reduced by a factor of 10). In some embodiments, a subject has a viral load decrease of 1 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >1 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.5 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 0.5 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.5 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.6 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 0.6 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.6 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.7 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 0.7 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.7 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.8 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 0.8 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.8 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.9 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 0.9 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >0.9 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >2 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 2 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >2 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >3 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 3 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >3 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >4 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 4 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >4 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >5 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of 5 logio copies/mL relative to baseline BK viral load. In some embodiments, a subject has a viral load decrease of >5 logio copies/mL relative to baseline BK viral load. [0465] In some embodiments, the disclosure provides a method of treatment comprising administering a composition comprising a polyclonal population of VSTs described herein to a patient, wherein the patient exhibits low or undetectable pre-existing immunity to BK virus or BK viral antigens prior to administration of the composition. In some embodiments, the treatment reduces BK viral load. In some embodiments, the treatment results in a reduction of BK viral load to a greater extent than a patient with low or undetectable immunity to BK virus or BK viral antigens in receipt of the placebo rather than the study drug.

[0466] In some embodiments, the disclosure provides a method of treatment comprising administering a composition comprising a polyclonal population of VSTs described herein to a patient, wherein the patient exhibits low or undetectable pre-existing immunity to BK virus or BK viral antigens prior to administration of the composition, and wherein the population of VSTs matches on more than three HLA alleles to the solid organ transplant. In some embodiments, the treatment results in a reduction of BK viral load to a greater extent than a patient administered a population of VSTs with matches on three or less HLA alleles to the solid organ transplant.

[0467] In some embodiments, the disclosure provides a method of treating a patient with low or undetectable pre-existing immunity to BK virus or BK viral antigen, wherein the treatment comprises administering a composition comprising a polyclonal population of VSTs described herein. In some embodiments, the disclosure provides a method of treatment of a patient with low or undetectable pre-existing immunity to BK virus or BK viral antigen, wherein the treatment comprises administering a composition comprising a polyclonal population of VSTs described herein, and wherein the treatment reduces BK viral load. In some embodiments, the treatment reduces BK viral load to a greater extent than treatment of a patient that exhibits pre-existing immunity to BK virus or BK viral antigens prior to treatment.

[0468] In some embodiments, the disclosure provides a method of treatment of a patient with low or undetectable pre-existing immunity to BK virus or BK viral antigen, wherein the treatment comprises administering a composition comprising a polyclonal population of VSTs described herein, wherein the treatment reduces BK viral load, and wherein the population of VSTs matches on more than three HLA alleles to the solid organ transplant. In some embodiments, the treatment with a population of VSTs reduces BK viral load to a greater extent than treatment of a patient that exhibits pre-existing immunity to BK virus or BK viral antigens prior to treatment, wherein the the population of VSTs matches on more than three HLA alleles to the solid organ transplant.

[0469] In some embodiments, immunity is measured by ELISpot assay where low ZFNy binding demonstrates low (<5 SFC/5xl0e5 PBMCs) or undetectable immunity and high binding demonstrates pre-existing immunity (defined as >5 SFC/5xl0e5 PBMCs). [0470] In some embodiments, the method results in a reduction of BK viral load to undetectable levels. In some embodiments, the method results in a reduction of BK viral load to undetectable levels, wherein viral load is measured by quantitation of viremia by PCR assay. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year. In some embodiments, the method results in reduction of BK viral load to undetectable levels for about 8 weeks to about 12 weeks. In some embodiments, the method results in reduction of BK viral load to undetectable levels for about 12 weeks to about 1 year. In some embodiments, the method results in reduction of BK viral load to undetectable levels for about 12 weeks to about 52 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 1 week. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 2 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 3 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 4 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 5 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 6 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 7 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 8 weeks. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 3 months. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 4 months. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 5 months. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 6 months. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 9 months. In some embodiments, the method results in a reduction of BK viral load to undetectable levels for at least 1 year.

[0471] In some embodiments, the method results in BK viremia remission. In some embodiments, the method results in longer BK viremia remission compared to BK viremia remission in a subject that received placebo treatment. BK viremia remission is defined as the length of time from the clearance of BK viremia to the reappearance of detectable BK viremia. In some embodiments, method results in a longer time of BK viremia remission compared to the BK viremia remission in a subject that received a placebo treatment, wherein the BK viremia remission is defined as the length of time from the clearance of BK viremia to reappearance of detectable BK viremia.

[0472] In some embodiments, BK viremia remission is 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 2 years, 3 years, 4 years, or more.

[0473] In some embodiments, the method results in a reduction in the incidence of recrudescent or new infections with one or more viruses compared to the incidence of recrudescent or new infections with the one or more viruses in a subject who received a placebo treatment. In some embodiments, the recrudescent or new infection is one or more of BKV, CMV, EBV, AdV, JCV, HHV6, or any combination thereof. In some embodiments, the recrudescent or new infection is one or more of CMV, EBV, AdV, JCV, HHV6, or any combination thereof. In some embodiments, the recrudescent or new infection is BKV.

[0474] In some embodiments, viral load is measured by a method known to those of skill in the art. Methods include, but are not limited to RT-PCR assay and branched DNA assay. In some embodiments, viral load is measured by RT-PCR assay. In some embodiments, viral load is measured by branched DNA assay. In some embodiments, viral load is measured from a blood sample.

[0475] In some embodiments, the BK viral load is confirmed by testing prior to administration of the composition.

[0476] In some embodiments, the method results in reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject compared to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in the subject prior to administration of a composition described herein (e.g. a composition comprising a polyclonal population of VSTs). In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 10%, about 25%, about 50%, about 75%, about 90%, or more relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 10% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 20% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 30% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 40% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 50% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 60% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 70% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 80% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 90% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 95% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 99% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein.

[0477] In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced compared to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject prior to administration of a composition described herein. In some embodiments, the method results in a mean loglO change in viral load of about -0.5 from baseline. In some embodiments, the method results in a mean log 10 change in viral load of about -0.5 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, the method results in a mean loglO change in viral load of about -1.0 from baseline. In some embodiments, the method results in a mean loglO change in viral load of about -1.0 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, the method results in a mean loglO change in viral load of about -1.5 from baseline. In some embodiments, the method results in a mean loglO change in viral load of about -1.5 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -0.25 from baseline. In some embodiments, the method results in a median loglO change in viral load of about -0.25 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -0.5 from baseline. In some embodiments, the method results in a median loglO change in viral load of about -0.5 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -1.0 from baseline. In some embodiments, the method results in a median loglO change in viral load of about -1.0 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein. In some embodiments, the method results in a median loglO change in viral load of about -1.5 from baseline. In some embodiments, the method results in a median log 10 change in viral load of about -1.5 from baseline, wherein baseline is one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load prior to administration of a composition described herein.

[0478] In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject compared to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, placebo treatment is cry opreservation media without cells. In some embodiments, placebo treatment is administered in the same volume as the treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by about 10%, about 25%, about 50%, about 75%, about 90%, or more relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 10% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 20% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 30% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 40% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 50% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 60% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 70% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 80% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 90% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 95% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject is reduced by at least 99% relative to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load of a subject who received a placebo treatment.

[0479] In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels, wherein viral load is measured by quantitation of viremia by PCR assay. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year . In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 1 week. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 2 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 3 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 4 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 5 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 6 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 7 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 8 weeks. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 3 months. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 4 months. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 5 months. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 6 months. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 9 months. In some embodiments, the method results in a reduction of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viral load to undetectable levels for at least 1 year.

[0480] In some embodiments, the method results in one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission. In some embodiments, the method results in longer one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission compared to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission in a subject that received placebo treatment. In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission is defined as the length of time from the clearance of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia to the reappearance of detectable one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, method results in a longer time of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission compared to one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission in a subject that received a placebo treatment, wherein one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission is defined as the length of time from the clearance of one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia to reappearance of detectable one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia.

[0481] In some embodiments, one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia remission is 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 2 years, 3 years, 4 years, or more. [0482] In some embodiments, the polyclonal population of VSTs circulate in the subject for at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, at least 15 weeks, at least 16 weeks, at least 17 weeks, or at least 18 weeks, inclusive of all ranges and subranges therebetween. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 9 weeks. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 10 weeks. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 11 weeks. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 12 weeks. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 13 weeks. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 14 weeks. In some embodiments, the polyclonal population of VSTs circulate in the recipient for at least 15 weeks.

[0483] In some embodiments of the disclosure, the generated polyclonal population of VSTs are provided to an individual that has or is at risk of having a pathogenic infection, including a viral, bacterial, or fungal infection. The individual may or may not have a deficient immune system. In some cases, the individual is at risk of a viral, bacterial, or fungal infection following organ or stem cell transplant (including hematopoietic stem cell transplantation), or has cancer or has been or will be subjected to cancer treatment, for example. In some cases the individual has an acquired immune system deficiency. In some embodiments, the individual is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant.

[0484] In some embodiments, the patient is at a higher risk than an average person in the general population of contracting a viral infection or viral disease or of having a latent virus reactivate. In some embodiments, the viral infection or viral disease or reactivation of a latent virus poses a greater risk to the patient’s health compared to the risk that such an infection or reactivation would pose to an average person in the general population. In some embodiments, the patient is immunocompromised. As used herein, immunocompromised means having a weakened immune system. For example, patients who are immunocompromised have a reduced ability to fight infections and other diseases. In some embodiments, the patient is immunocompromised due to a treatment the patient received to treat the disease or condition or another disease or condition. In some embodiments, the patient is immunocompromised due to age. In some embodiments, the patient is immunocompromised due to young age. For example, In some embodiments, the patient is less than 1 year of age. In some embodiments, the patient is immunocompromised due to old age. For example, in some embodiments, the patent is over 60 years of age, over 65 years of age, over 70 years of age, over 75 years of age, over 80 years of age, or over 85 years of age. In some embodiments, the patient is immunocompromised due to young or old age coupled with an immune deficiency. In some embodiments, the patient is in need of a transplant therapy. In some embodiments, the patient is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the patient received a kidney transplant.

[0485] In some embodiments, a subject is administered about IxlO ⁷ , about 2xl0 ⁷ , about 3xl0 ⁷ , about 4xl0 ⁷ , about 5xl0 ⁷ , about 6xl0 ⁷ , about 7xl0 ⁷ , about 8xl0 ⁷ , about 9xl0 ⁷ , about IxlO ⁸ , about l. lxlO ⁸ , about 1.2xl0 ⁸ , about 1.3xl0 ⁸ , about 1.4xl0 ⁸ , about 1.5xl0 ⁸ , or about 1.6xl0 ⁸ VSTs. In some embodiments, a subject is administered about IxlO ⁷ , about 2xl0 ⁷ , about 3xl0 ⁷ , about 4xl0 ⁷ , about 5xl0 ⁷ , about 6xl0 ⁷ , about 7xl0 ⁷ , about 8xl0 ⁷ , about 9xl0 ⁷ , about IxlO ⁸ , about l.lxlO ⁸ , about 1.2xl0 ⁸ , about 1.3xl0 ⁸ , about 1.4xl0 ⁸ , about 1.5xl0 ⁸ , or about 1.6xl0 ⁸ VSTs per administration (e.g., per infusion). In some embodiments, a subject is administered about about 4xl0 ⁷ VSTs. In some embodiments, a subject is administered about 4xl0 ⁷ VSTs per administration (e.g., per infusion). In some embodiments, a subject is administered IxlO ⁷ , about 2xl0 ⁷ , about 3xl0 ⁷ , about 4xl0 ⁷ , about 5xl0 ⁷ , about 6xl0 ⁷ , about 7xl0 ⁷ , about 8xl0 ⁷ , about 9xl0 ⁷ , about IxlO ⁸ , about l.lxlO ⁸ , about 1.2xl0 ⁸ , about 1.3xl0 ⁸ , about 1.4xl0 ⁸ , about 1.5xl0 ⁸ , or about 1.6xl0 ⁸ Posoleucel cells. In some embodiments, a subject is administered about IxlO ⁷ , about 2xl0 ⁷ , about 3xl0 ⁷ , about 4xl0 ⁷ , about 5xl0 ⁷ , about 6xl0 ⁷ , about 7xl0 ⁷ , about 8xl0 ⁷ , about 9xl0 ⁷ , about IxlO ⁸ , about l.lxlO ⁸ , about 1.2xl0 ⁸ , about 1.3xl0 ⁸ , about 1.4xl0 ⁸ , or about 1.5xl0 ⁸ , or about 1.6xl0 ⁸ Posoleucel cells per administration e.g., per infusion). In some embodiments, a subject is administered 4xl0 ⁷ Posoleucel cells. In some embodiments, a subject is administered 4xl0 ⁷ Posoleucel cells per administration (e.g., per infusion).

[0486] In some embodiments, the composition is administered to a subject at a dose of about IxlO ⁶ VSTs, about 2xl0 ⁶ VSTs, about 3xl0 ⁶ VSTs, about 4xl0 ⁶ VSTs, about 5xl0 ⁶ VSTs, about 6xl0 ⁶ VSTs, about 7xl0 ⁶ VSTs, about 8xl0 ⁶ VSTs, about 9xl0 ⁶ VSTs, about IxlO ⁷ VSTs, about 2xl0 ⁷ VSTs, about 3xl0 ⁷ VSTs, about 4xl0 ⁷ VSTs, about 5xl0 ⁷ VSTs, about 6xl0 ⁷ VSTs, about 7xl0 ⁷ VSTs, about 8xl0 ⁷ VSTs, about 9xl0 ⁷ VSTs, about IxlO ⁸ VSTs, about l. lxlO ⁸ VSTs, about 1.2xl0 ⁸ VSTs, about 1.3xl0 ⁸ VSTs, about 1.4xl0 ⁸ VSTs, about 1.5xlO ⁸ VSTs, or about 1.6xl0 ⁸ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 5xl0 ⁶ VSTs to about 2xl0 ⁷ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 2xl0 ⁷ VSTs to about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 1.2xl0 ⁷ VSTs to about 5xl0 ⁷ VSTs.

[0487] In some embodiments, the composition is administered to a subject at a dose of about IxlO ⁷ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 2xl0 ⁷ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 4xl0 ⁷ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to a subject at a dose of about IxlO ⁸ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 1.2xl0 ⁸ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 1.4xl0 ⁸ VSTs. In some embodiments, the composition is administered to a subject at a dose of about 1.6xl0 ⁸ VSTs.

[0488] In some embodiments, administered VSTs persist in a subject. In some embodiments, administered VSTs persist in a subject for at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks from baseline. In some embodiments, administered VSTs persist in a subject for at least 24 weeks from baseline. In some embodiments, administered VSTs persist in a subject for at least 12 weeks from baseline. In some embodiments, administered VSTs persist in a subject for at least 4 weeks from baseline.

[0489] In some embodiments, administered VSTs persist in a subject for at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks from the final administration of a composition comprising VSTs. In some embodiments, administered VSTs persist in a subject for at least 12 weeks from final administration of a composition comprising VSTs.

[0490] In some embodiments, administration of a composition comprising a polyclonal population of VSTs results in circulating functional BK specific T cells. In some embodiments, functional BK specific T cells circulate in a subject for at least at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks from baseline. In some embodiments, functional BK specific T cells circulate in a subject for at least 24 weeks from baseline. In some embodiments, functional BK specific T cells circulate in a subject for at least 12 weeks from baseline. In some embodiments, functional BK specific T cells circulate in a subject for at least 4 weeks from baseline.

[0491] In some embodiments, the functional BK specific T cells circulate in a subject for at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, the functional BK specific T cells circulate in a subject for at least 4 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, the functional BK specific T cells circulate in a subject for at least 12 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, the functional BK specific T cells circulate in a subject for at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation. [0492] In some embodiments, administration of a composition comprising a polyclonal population of VSTs results in circulating functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV). In some embodiments, functional BK specific T cells circulate in a subject for at least at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks from baseline. In some embodiments, functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 24 weeks from baseline. In some embodiments, functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 12 weeks from baseline. In some embodiments, functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 4 weeks from baseline.

[0493] In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 4 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 12 weeks after the BK viral load is reduced below the lower limit of quantitation. In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 24 weeks after the BK viral load is reduced below the lower limit of quantitation.

[0494] In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 24 weeks after the viral load of one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 is reduced below the lower limit of quantitation. In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 4 weeks after the BK viral load of one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 is reduced below the lower limit of quantitation. In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 12 weeks after the viral load of one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 is reduced below the lower limit of quantitation. In some embodiments, the functional T cells specific for BKV, CMV, EBV, AdV, and/or HHV6 (with cross-reactivity for JCV) circulate in a subject for at least 24 weeks after the viral load of one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 is reduced below the lower limit of quantitation.

[0495] In some embodiments, the primary immune deficiency disease (PIDD) may be a genetic disorder. Exemplary PIDDs include autoimmune lymphoproliferative syndrome (ALPS), autoimmune polyglandular syndrome type 1 APS-1), BENTA disease, caspase 8 deficiency state, CARD9 deficiency, chronic granulomatous disease (CGD), common variable immuonodeficiency, congenital neutropenia syndromes, CTLA4 deficiency, DOCK8 deficiency, GATA2 deficiency, glycosylation disorders, hyper-immunoglobulin E syndromes, hyper-immunoglobulin M syndromes, cytokine deficiencies, leukocyte adhesion deficiency, LRBA deficiency, PI3 kinase disease, PCLG2-associated antibody deficiency and immune dysregulation (PLAID), severe combined immunodeficiency (SCID), STAT3 dominant negative disease, STAT3 gain of function disease, WHIM syndrome, Wiskott- Aldrich syndrome, X-linked agammaglobulinemia, X-linked lymphoproliferative disease, XMEN disease, complement deficiency, selective IgA deficiency, DiGeorge syndrome, and ataxia-telangectasia. In some embodiments, the patient has an immune deficiency disease that is not a PIDD, for example, an HIV infection and/or acquired immunodeficiency syndrome (AIDS).

[0496] In some embodiments, the subject has one or more subsequent viral infections or viral disease. In some embodiments, the subject has one or more subsequent viral infections or viral disease at the time of administration of a composition described herein. In some embodiments, the subsequent viral infection is one or more of BK virus, CMV, AdV, EBV, JCV, and/or HHV6, or any combination thereof. In some embodiments, the subsequent viral infection is BK virus and one or more of CMV, AdV, EBV, JCV, and/or HHV6. In some embodiments, the method results in a reduction or prevention of subsequent viral infections in a subject with one or more viruses. In some embodiments, the method results in a reduction of subsequent viral infections or viral disease in a subject with one or more viruses. In some embodiments, the method results in a prevention of subsequent viral infections or viral disease in a subject with one or more viruses.

[0497] In some embodiments, the method of treatment reduces viral load of the one or more concomitant viral infections by about 10%, about 25%, about 50%, about 75%, about 90%, or more. In some embodiments, the method of treatment reduces viral load of the one or more concomitant viral infections by about 10%, about 25%, about 50%, about 75%, about 90%, or more, wherein the viral load is measured by quantitation of viremia and/or viruria by PCR assay.

[0498] In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered subsequent to administration of an analgesic and an antihistamine. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered subsequent to administration of diphenhydramine and acetaminophen. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered subsequent to administration of an analgesic. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered subsequent to administration of acetaminophen. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered subsequent to administration of an antihistamine. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered subsequent to diphenhydramine.

[0499] In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered in combination with administration of an analgesic and an antihistamine. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered in combination with administration of diphenhydramine and acetaminophen. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered in combination with administration of an analgesic. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered in combination with administration of acetaminophen. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered in combination with administration of an antihistamine. In some embodiments, a composition comprising a polyclonal population of VSTs as described herein is administered in combination with diphenhydramine.

[0500] In some embodiments the dose of antihistamine is about 0.25 mg/kg to about 0.5 mg/kg. In some embodiments the dose of antihistamine is about 0.1 mg/kg to about 0.7 mg/kg. In some embodiments the dose of antihistamine is about 0. 15 mg/kg. In some embodiments the dose of antihistamine is about 0.20 mg/kg. In some embodiments the dose of antihistamine is about 0.25 mg/kg. In some embodiments the dose of antihistamine is about 0.30 mg/kg. In some embodiments the dose of antihistamine is about 0.35 mg/kg. In some embodiments the dose of antihistamine is about 0.40 mg/kg. In some embodiments the dose of antihistamine is about 0.45 mg/kg. In some embodiments the dose of antihistamine is about 0.50 mg/kg. In some embodiments the dose of antihistamine is about 0.55 mg/kg. In some embodiments the dose of antihistamine is about 0.60 mg/kg. In some embodiments the dose of antihistamine is about 0.65 mg/kg.

[0501] In some embodiments the dose of diphenhydramine is about 0.25 mg/kg to about 0.5 mg/kg. In some embodiments the dose of diphenhydramine is about 0.1 mg/kg to about 0.7 mg/kg. In some embodiments the dose of diphenhydramine is about 0. 15 mg/kg. In some embodiments the dose of diphenhydramine is about 0.15 mg/kg. In some embodiments the dose of diphenhydramine is about 0.20 mg/kg. In some embodiments the dose of diphenhydramine is about 0.25 mg/kg. In some embodiments the dose of diphenhydramine is about 0.30 mg/kg. In some embodiments the dose of diphenhydramine is about 0.35 mg/kg. In some embodiments the dose of diphenhydramine is about 0.40 mg/kg. In some embodiments the dose of diphenhydramine is about 0.45 mg/kg. In some embodiments the dose of diphenhydramine is about 0.50 mg/kg. In some embodiments the dose of diphenhydramine is about 0.55 mg/kg. In some embodiments the dose of diphenhydramine is about 0.60 mg/kg. In some embodiments the dose of diphenhydramine is about 0.65 mg/kg. In some embodiments the dose of diphenhydramine is about 0.70 mg/kg.

[0502] In some embodiments, the dose of antihistamine does not exceed 22 mg. In some embodiments, the dose of antihistamine does not exceed 23 mg. In some embodiments, the dose of antihistamine does not exceed 24 mg. In some embodiments, the dose of antihistamine does not exceed 25 mg. In some embodiments, the dose of antihistamine does not exceed 26 mg. In some embodiments, the dose of antihistamine does not exceed 27 mg. In some embodiments, the dose of antihistamine does not exceed 28 mg.

[0503] In some embodiments, the dose of diphenhydramine does not exceed 22 mg. In some embodiments, the dose of diphenhydramine does not exceed 23 mg. In some embodiments, the dose of diphenhydramine does not exceed 24 mg. In some embodiments, the dose of diphenhydramine does not exceed 25 mg. In some embodiments, the dose of diphenhydramine does not exceed 26 mg. In some embodiments, the dose of diphenhydramine does not exceed 27 mg. In some embodiments, the dose of diphenhydramine does not exceed 28 mg.

[0504] In some embodiments, the antihistamine is administered intravenously or orally. In some embodiments, the antihistamine is administered intravenously. In some embodiments, the antihistamine is administered orally. In some embodiments, the diphenhydramine is administered intravenously or orally. In some embodiments, the diphenhydramine is administered intravenously. In some embodiments, the diphenhydramine is administered orally.

[0505] In some embodiments, the dose of analgesic is about 1 mg/kg to about 15 mg/kg. In some embodiments, the dose of analgesic is about 5 mg/kg to about 10 mg/kg. In some embodiments, the dose of analgesic is about 1 mg/kg. In some embodiments, the dose of analgesic is about 2 mg/kg. In some embodiments, the dose of analgesic is about 3 mg/kg. In some embodiments, the dose of analgesic is about 4 mg/kg. In some embodiments, the dose of analgesic is about 5 mg/kg. In some embodiments, the dose of analgesic is about 6 mg/kg. In some embodiments, the dose of analgesic is about 7 mg/kg. In some embodiments, the dose of analgesic is about 8 mg/kg. In some embodiments, the dose of analgesic is about 9 mg/kg. In some embodiments, the dose of analgesic is about 10 mg/kg. In some embodiments, the dose of analgesic is about 11 mg/kg. In some embodiments, the dose of analgesic is about 12 mg/kg. In some embodiments, the dose of analgesic is about 13 mg/kg. In some embodiments, the dose of analgesic is about 14 mg/kg. In some embodiments, the dose of analgesic is about 15 mg/kg.

[0506] In some embodiments, the dose of acetaminophen is about 1 mg/kg to about 15 mg/kg. In some embodiments, the dose of acetaminophen is about 5 mg/kg to about 10 mg/kg. In some embodiments, the dose of acetaminophen is about 1 mg/kg. In some embodiments, the dose of acetaminophen is about 2 mg/kg. In some embodiments, the dose of acetaminophen is about 3 mg/kg. In some embodiments, the dose of acetaminophen is about 4 mg/kg. In some embodiments, the dose of acetaminophen is about 5 mg/kg. In some embodiments, the dose of acetaminophen is about 6 mg/kg. In some embodiments, the dose of acetaminophen is about 7 mg/kg. In some embodiments, the dose of acetaminophen is about 8 mg/kg. In some embodiments, the dose of acetaminophen is about 9 mg/kg. In some embodiments, the dose of acetaminophen is about 10 mg/kg. In some embodiments, the dose of acetaminophen is about 11 mg/kg. In some embodiments, the dose of acetaminophen is about 12 mg/kg. In some embodiments, the dose of acetaminophen is about 13 mg/kg. In some embodiments, the dose of acetaminophen is about 14 mg/kg. In some embodiments, the dose of acetaminophen is about 15 mg/kg.

[0507] In some embodiments, the dose of analgesic does not exceed 600 mg. In some embodiments, the dose of analgesic does not exceed 610 mg. In some embodiments, the dose of analgesic does not exceed 620 mg. In some embodiments, the dose of analgesic does not exceed 630 mg. In some embodiments, the dose of analgesic does not exceed 640 mg. In some embodiments, the dose of analgesic does not exceed 650 mg.

[0508] In some embodiments, the dose of acetaminophen does not exceed 600 mg. In some embodiments, the dose of acetaminophen does not exceed 610 mg. In some embodiments, the dose of acetaminophen does not exceed 620 mg. In some embodiments, the dose of acetaminophen does not exceed 630 mg. In some embodiments, the dose of acetaminophen does not exceed 640 mg. In some embodiments, the dose of acetaminophen does not exceed 650 mg.

[0509] In some embodiments, the analgesic is administered intravenously or orally. In some embodiments, the analgesic is administered intravenously. In some embodiments, the analgesic is administered orally. In some embodiments, the acetaminophen is administered intravenously or orally. In some embodiments, the acetaminophen is administered intravenously. In some embodiments, the acetaminophen is administered orally.

[0510] In some embodiments, the antihistamine and analgesic are administered intravenously. In some embodiments, the antihistamine and analgesic are administered orally. In some embodiments, the antihistamine is administered orally, and the analgesic is administered intravenously. In some embodiments, the analgesic is administered orally, and the antihistamine is administered intravenously.

[0511] In some embodiments, the diphenhydramine and acetaminophen are administered intravenously. In some embodiments, the diphenhydramine and acetaminophen are administered orally. In some embodiments, the diphenhydramine is administered orally, and the acetaminophen is administered intravenously. In some embodiments, the acetaminophen is administered orally, and the diphenhydramine is administered intravenously.

[0512] In some embodiments, the subject has not been administered abatacept and/or belatacept within three months of screening.

[0513] In some embodiments, the subject has not been administered abatacept and/or belatacept within three months of screening.

[0514] In some embodiments, a subject is administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab. In some embodiments, a subject is administered corticosteroids, anti-thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab. In some embodiments, a subject is administered corticosteroids. In some embodiments, the corticosteroid is prednisone. In some embodiments, prednisone is not administered at a dose of greater than 0.5 mg/kg/day or equivalent.

[0515] In some embodiments, the subject is not administered anti -thymocyte globulin (ATG). In some embodiments, the subject is not administered anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg. In some embodiments, the subject has not been administered antithymocyte globulin (ATG) in doses of >4.5 mg/kg, alemtuzumab, or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days of treatment. In some embodiments, the subject has not been administered anti -thymocyte globulin (ATG) in doses of >4.5 mg/kg, alemtuzumab, or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days of randomization. In some embodiments a subject is administered alemtuzumab. [0516] In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 28 days of administration of a composition described herein (e.g. a composition comprising a polyclonal population of VSTs). In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 28 days of administration of a composition described herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, a subject is not administered corticosteroids within 28 days of administration of a composition described herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the subject is not administered anti -thymocyte globulin (ATG) within 28 days of administration of a composition described herein e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the subject is not administered anti-thymocyte globulin (ATG) in doses of > 4.5 mg/kg within 28 days of administration of a composition described herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments a subject is not administered alemtuzumab within 28 days of administration of a composition described herein (e.g., a composition comprising a polyclonal population of VSTs).

[0517] In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 28 days prior to administration of a composition described herein (e.g. a composition comprising a polyclonal population of VSTs). In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 28 days subsequent to administration of a composition described herein (e.g. a composition comprising a polyclonal population of VSTs).

[0518] In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 25 days of administration of a composition described herein. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 25 days of administration. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 26 days of administration of a composition described herein. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 26 days of administration. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 27 days of administration of a composition described herein. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 27 days of administration. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 28 days of administration of a composition described herein. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 28 days of administration. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 29 days of administration of a composition described herein. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 29 days of administration. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG), or alemtuzumab within 30 days of administration of a composition described herein. In some embodiments, a subject is not administered corticosteroids, anti -thymocyte globulin (ATG) in doses of > 4.5 mg/kg, or alemtuzumab within 30 days of administration.

[0519] In some embodiments, the subject is administered mycofenolate mofetil (MMF). In some embodiments, the subject is administered calcineurin. In some embodiments, the subject is administered mycofenolate mofetil (MMF) and/or calcineurin. In some embodiments, the subject is administered MPA (mycophenolic acid). In some embodiments, the subject is administered azathioprine. In some embodiments, the subject is administered an mTOR inhibitor.

[0520] In some embodiments, the method comprises administering MMF to a subject prior to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering MMF to a subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering calcineurin to a subject prior to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering calcineurin to a subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering MMF and calcineurin to a subject prior to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering MMF and calcineurin to a subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering MPA to a subject prior to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering MPA to a subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering azathioprine to a subject prior to administration of a composition herein e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering azathioprine to a subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering an mTOR inhibitor to a subject prior to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering an mTOR inhibitor to a subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs).

[0521] In some embodiments, the method comprises administering one or more antiviral agents to the subject. In some embodiments, the method comprises administering one or more antiviral agents to the subject prior to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering one or more antiviral agents to the subject subsequent to administration of a composition herein (e.g., a composition comprising a polyclonal population of VSTs). In some embodiments, the method comprises administering one antiviral agent to the subject. In some embodiments, the method comprises administering one two antiviral agents to the subject. In some embodiments, the method comprises administering three antiviral agent to the subject.

[0522] In some embodiments, the antiviral agent is selected from foscarnet and ganciclovir. In some embodiments, the antiviral agent is foscarnet. In some embodiments, the antiviral agent is ganciclovir. In some embodiments, the method comprises administering one or more antiviral agents selected from foscarnet and ganciclovir.

[0523] In some embodiments, a subject administered a composition described herein has stable immunosuppression (IS). In some embodiments, a subject administered a composition described herein has stable immunosuppression following solid organ transplant. In some embodiments, a subject has received stable immunosuppression following solid organ transplant. In some embodiments, a subject is receiving stable immunosuppression following solid organ transplant. In some embodiments, the solid organ transplant is a kidney transplant. In some embodiments, a subject administered a composition described herein has stable immunosuppression 10 weeks, 9 weeks, 8 weeks, 7 weeks, 6 weeks, 5 weeks, or 4 weeks prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression 5 weeks prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression 30 days prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression at least 10 weeks, at least 9 weeks, at least 8 weeks, at least 7 weeks, at least 6 weeks, at least 5 weeks, or at least 4 weeks prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression at least 5 weeks prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression for at least 30 days prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression about 10 weeks, about 9 weeks, about 8 weeks, about 7 weeks, about 6 weeks, about 5 weeks, or about 4 weeks prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression about 5 weeks prior to administration of the composition. In some embodiments, a subject administered a composition described herein has stable immunosuppression for about 30 days prior to administration of the composition.

[0524] In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction in treatment with an immune suppressing therapy. In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction in treatment with an immune suppressing therapy 30 (+/-2) days before randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction in treatment with an immune suppressing therapy within 30 (+/-2) days of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction in treatment with an immune suppressing therapy within about 4 weeks of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction in treatment with an immune suppressing therapy within about 5 weeks of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction in the dose of one or more immune suppressing therapies. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction in the dose of one or more immune suppressing therapies 30 (+/-2) days before randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction in the dose of one or more immune suppressing therapies within 30 (+/-2) days of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction in the dose of one or more immune suppressing therapies within about 4 weeks of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction in the dose of one or more immune suppressing therapies within about 5 weeks of randomization for treatment with a composition described herein. In some embodiments, the immunosuppression therapy is tacrolimus, cyclosporine, sirolimus, everolimus, mycophenolate, or Azathioprine. In some embodiments, stable immunosuppression is categorized as having less than 50% decrease in one or more of tacrolimus, cyclosporine, sirolimus, everolimus, mycophenolate, and Azathioprine. In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction in treatment with CNI (calcineurin inhibitor), an mTOR inhibitor, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction in treatment with CNI (calcineurin inhibitor), an mTOR inhibitor, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine within 30 days of treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having a less than 50% reduction of a patient’s major immunosuppressive regimen (z.e., CNI (calcineurin inhibitor), mTOR, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine) 30 (+/-2) days before randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction of a patient’s major immunosuppressive regimen (z.e., CNI (calcineurin inhibitor), mTOR, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine) within 30 (+/-2) days of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction of a patient’s major immunosuppressive regimen (z.e., CNI (calcineurin inhibitor), mTOR, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine) within about 4 weeks of randomization for treatment with a composition described herein. In some embodiments, stable immunosuppression is categorized as having less than 50% reduction of a patient’s major immunosuppressive regimen (z.e., CNI (calcineurin inhibitor), mTOR, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine) within about 5 weeks of randomization for treatment with a composition described herein.

[0525] In some embodiments, a subject does not have stable immunosuppression if they have a significant reduction in immunosuppression. In some embodiments, a significant reduction in immunosuppression is a greater than or equal to 50% reduction in the dose(s) of immunosuppressive medication at the time of study randomization compared to the dose(s) of immunosuppressive medication 30 days (+/- 2 days) before randomization. In some embodiments, a significant reduction in immunosuppression is defined by the subject switching immunosuppressive medication to a less potent medication, e.g., switching from tacrolimus to cyclosporine, tacrolimus to everolimu, tacrolimus to sirolimus, mycophenolate to everolimus, or mycophenolate to sirolimus. In some embodiments, the immunosuppressive medication is one or more of tacrolimus, Prografm Envarsus, Cyclosporine, Everolimus, Sirolimus, Mycophenolate, MPA, MMF, or Azathioprine. In some embodiments, a subject is not considered to have a reduction in immunosuppression if there is a decrease in one immunosuppressive medication by greater than or equal to 50% and a second immunosuppressive medication is increased by at least 50%. In some embodiments, a subject is not considered to have a reduction in immunosuppression if the subject started and stoppsed an immunosuppressive medication between 32 days and randomization day.

[0526] In some embodiments, the method comprises immunosuppression reduction. In some embodiments, the method comprises immunosuppression reduction in a patient who is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is 1,000 copies/mL to 5,000 copies/mL prior to administration of the composition. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is about 1,000 copies/mL to about 5,000 copies/mL prior to administration of the composition. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is 1,000 copies/mL to 5,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 5,000 about 14 days after the initial determination of the BK viral load. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is about 1,000 copies/mL to about 5,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 5,000 about 14 days after the initial determination of the BK viral load. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is 5,000 copies/mL to 10,000,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is 5,000 copies/mL to 50,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is about 5,000 copies/mL to about 50,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is about 5,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is greater than 5,000 copies/mL.

[0527] In some embodiments, the method comprises immunosuppression reduction. In some embodiments, the method comprises immunosuppression reduction in a patient who is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is 1,000 copies/mL to 10,000 copies/mL prior to administration of the composition. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is about 1,000 copies/mL to about 10,000 copies/mL prior to administration of the composition. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is 1,000 copies/mL to 10,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 10,000 about 14 days after the initial determination of the BK viral load. In some embodiments, the method comprises immunosuppression reduction if the subjects BK viral load is about 1,000 copies/mL to about 10,000 copies/mL prior to administration of the composition and the subject’s BK viral load is greater than 10,000 about 14 days after the initial determination of the BK viral load. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is 10,000 copies/mL to 50,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is about 10,000 copies/mL to about 50,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is 10,000 copies/mL to 10,000,000 copies/mL. In In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is greater than about 10,000 copies/mL to about 10,000,000 copies/mL. In some embodiments, the method comprises immunosuppression reduction if the subject’s BK viral load prior to administration of the composition is greater than 10,000 copies/mL.

[0528] In some embodiments, the immunosuppression reduction comprises reducing in administration of MMF. In some embodiments, the immunosuppression reduction comprises reducing administration of MMF by up to 50% of the starting dose of MMF. In some embodiments, the immunosuppression reduction comprises reducing administration of MMF by up to 40% of the starting dose of MMF. In some embodiments, the immunosuppression reduction comprises reducing administration of MMF by up to 30% of the starting dose of MMF. In some embodiments, the immunosuppression reduction comprises reducing administration of MMF by up to 20% of the starting dose of MMF. In some embodiments, the immunosuppression reduction comprises reducing administration of MMF by up to 10% of the starting dose of MMF.

[0529] In some embodiments, the immunosuppression reduction comprises reducing in administration of calcineurin inhibitors. In some embodiments, the immunosuppression reduction comprises reducing administration of calcineurin inhibitors by up to 50% of the starting dose of calcineurin inhibitors. In some embodiments, the immunosuppression reduction comprises reducing administration of calcineurin inhibitors by up to 40% of the starting dose of calcineurin inhibitors. In some embodiments, the immunosuppression reduction comprises reducing administration of calcineurin inhibitors by up to 30% of the starting dose of calcineurin inhibitors. In some embodiments, the immunosuppression reduction comprises reducing administration of calcineurin inhibitors by up to 20% of the starting dose of calcineurin inhibitors. In some embodiments, the immunosuppression reduction comprises reducing administration of calcineurin inhibitors by up to 10% of the starting dose of calcineurin inhibitors. [0001] In some embodiments, the immunosuppression reduction comprises reducing in administration of corticosteroids. In some embodiments, the immunosuppression reduction comprises reducing administration of corticosteroids by up to 50% of the starting dose of corticosteroids. In some embodiments, the immunosuppression reduction comprises reducing administration of corticosteroids by up to 40% of the starting dose of corticosteroids. In some embodiments, the immunosuppression reduction comprises reducing administration of corticosteroids by up to 30% of the starting dose of corticosteroids. In some embodiments, the immunosuppression reduction comprises reducing administration of corticosteroids by up to 20% of the starting dose of corticosteroids. In some embodiments, the immunosuppression reduction comprises reducing administration of corticosteroids by up to 10% of the starting dose of corticosteroids.

[0530] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, a subject having BK viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in one or more of the following:

(i) a reduction in the frequency and/or severity of biopsy-proven acute allograft rejection in the population compared with a population of subjects that receive no treatment or a placebo treatment;

(ii) a reduction in the number of subjects with urinary polyomavirus haufen compared with a population of subjects that receive no treatment or a placebo treatment;

(iii) a reduction in the time to resolution of non-BK viral infections compared with that in a population of subjects that receive no treatment or a placebo treatment;

(iv) a reduction in the use of immunosuppressive agents in the subjects’ treatment regimens, compared with a population of subjects that receive no treatment or a placebo treatment;

(v) a reduction in the number of hospitalizations and/or re-hospitalizations and/or a reduction in the number of days hospitalized in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(vi) a reduction in the incidence and/or duration of use of any other antiviral therapies during the study in the population, compared with a population of subjects that receive no treatment or a placebo treatment;

(vii) an increase in the time to death in the population, compared with a population of subjects that receive no treatment or a placebo treatment;

(viii) a decrease in the number of subjects in the population with kidney injury requiring hemodialysis, compared with a population of subjects that receive no treatment or a placebo treatment;

(ix) an improvement in the rate of decline of BK viremia in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(x) an increase in the mean and/or median eGFR in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(xi) a reduction in the frequency of subjects who experience GVHD, compared with a population of subjects that receive no treatment or a placebo treatment;

(xii) an increase in the rate of kidney allograft survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment; and

(xiii) an increase in the rate of survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0531] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, a subject having BK viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the frequency and/or severity of biopsy -proven acute allograft rejection in the population compared with a population of subjects that receive no treatment or a placebo treatment.

[0532] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results a reduction in the number of subjects with urinary polyomavirus haufen compared with a population of subjects that receive no treatment or a placebo treatment.

[0533] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the time to resolution of non-BK viral infections compared with that in a population of subjects that receive no treatment or a placebo treatment.

[0534] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the use of immunosuppressive agents in the subjects’ treatment regimens, compared with a population of subjects that receive no treatment or a placebo treatment.

[0535] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the number of hospitalizations and/or re-hospitalizations and/or a reduction in the number of days hospitalized in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

[0536] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the incidence and/or duration of use of any other antiviral therapies during the study in the population, compared with a population of subjects that receive no treatment or a placebo treatment. [0537] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in an increase in the time to death in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0538] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a decrease in the number of subjects in the population with kidney injury requiring hemodialysis, compared with a population of subjects that receive no treatment or a placebo treatment.

[0539] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in an improvement in the rate of decline of BK viremia in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment.

[0540] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in an increase in the mean and/or median eGFR in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

[0541] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, a subject having BK viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the frequency of subjects who experience GVHD, compared with a population of subjects that receive no treatment or a placebo treatment.

[0542] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, a subject having BK viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in an increase in the rate of kidney allograft survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having BK viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in an increase in the rate of survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0543] In some embodiments, the method comprises treating a population of subjects having BK virus associated nephropathy (BKV AN). In some embodiments, a subject having BKV AN is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having BKV AN, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in one or more of the following:

(i) a reduction in the frequency and/or severity of biopsy-proven acute allograft rejection in the population compared with a population of subjects that receive no treatment or a placebo treatment;

(ii) a reduction in the number of subjects with urinary polyomavirus haufen compared with a population of subjects that receive no treatment or a placebo treatment;

(iii) a reduction in the time to resolution of non-BK viral infections compared with that in a population of subjects that receive no treatment or a placebo treatment;

(iv) a reduction in the use of immunosuppressive agents in the subjects’ treatment regimens, compared with a population of subjects that receive no treatment or a placebo treatment;

(v) a reduction in the number of hospitalizations and/or re-hospitalizations and/or a reduction in the number of days hospitalized in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(vi) a reduction in the incidence and/or duration of use of any other antiviral therapies during the study in the population, compared with a population of subjects that receive no treatment or a placebo treatment;

(vii) an increase in the time to death in the population, compared with a population of subjects that receive no treatment or a placebo treatment;

(viii) a decrease in the number of subjects in the population with kidney injury requiring hemodialysis, compared with a population of subjects that receive no treatment or a placebo treatment;

(ix) an improvement in the rate of decline of BK viremia in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(x) an increase in the mean and/or median eGFR in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(xi) a reduction in the frequency of subjects who experience GVHD, compared with a population of subjects that receive no treatment or a placebo treatment;

(xii) an increase in the rate of kidney allograft survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment; and

(xiii) an increase in the rate of survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0544] In some embodiments, the method comprises treating a population of subjects having BKVAN. In some embodiments, the method comprises treating a population of subjects having BKVAN, wherein the subjects are the recipients of a solid organ transplant, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from BK virus (BKV), wherein the method results in a reduction in the frequency and/or severity of biopsy -proven acute allograft rejection in the population compared with a population of subjects that receive no treatment or a placebo treatment.

[0545] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, a subject having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in one or more of the following:

(i) a reduction in the frequency and/or severity of biopsy-proven acute allograft rejection in the population compared with a population of subjects that receive no treatment or a placebo treatment;

(ii) a reduction in the number of subjects with urinary polyomavirus haufen compared with a population of subjects that receive no treatment or a placebo treatment;

(iii) a reduction in the time to resolution of CMV, EBV, AdV, JCV, and/or HHV6 viral infections compared with that in a population of subjects that receive no treatment or a placebo treatment;

(iv) a reduction in the use of immunosuppressive agents in the subjects’ treatment regimens, compared with a population of subjects that receive no treatment or a placebo treatment;

(v) a reduction in the number of hospitalizations and/or re-hospitalizations and/or a reduction in the number of days hospitalized in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(vi) a reduction in the incidence and/or duration of use of any other antiviral therapies during the study in the population, compared with a population of subjects that receive no treatment or a placebo treatment;

(vii) an increase in the time to death in the population, compared with a population of subjects that receive no treatment or a placebo treatment; (viii) a decrease in the number of subjects in the population with kidney injury requiring hemodialysis, compared with a population of subjects that receive no treatment or a placebo treatment;

(ix) an improvement in the rate of decline of one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(x) an increase in the mean and/or median eGFR in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

(xi) a reduction in the frequency of subjects who experience GVHD, compared with a population of subjects that receive no treatment or a placebo treatment;

(xii) an increase in the rate of kidney allograft survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment; and

(xiii) an increase in the rate of survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0546] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, a subject having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in a reduction in the frequency and/or severity of biopsy- proven acute allograft rejection in the population compared with a population of subjects that receive no treatment or a placebo treatment.

[0547] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 virus, wherein the method results a reduction in the number of subjects with urinary polyomavirus haufen compared with a population of subjects that receive no treatment or a placebo treatment.

[0548] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 virus, wherein the method results in a reduction in the time to resolution of non-one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral infections compared with that in a population of subjects that receive no treatment or a placebo treatment.

[0549] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 virus, wherein the method results in a reduction in the use of immunosuppressive agents in the subjects’ treatment regimens, compared with a population of subjects that receive no treatment or a placebo treatment.

[0550] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in a reduction in the number of hospitalizations and/or re-hospitalizations and/or a reduction in the number of days hospitalized in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment; [0551] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in a reduction in the incidence and/or duration of use of any other antiviral therapies during the study in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0552] In some embodiments, the method comprises treating a population of subjects having BK viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in an increase in the time to death in the population, compared with a population of subjects that receive no treatment or a placebo treatment. [0553] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in a decrease in the number of subjects in the population with kidney injury requiring hemodialysis, compared with a population of subjects that receive no treatment or a placebo treatment.

[0554] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in an improvement in the rate of decline of BK viremia in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment.

[0555] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in an increase in the mean and/or median eGFR in the population of subjects, compared with a population of subjects that receive no treatment or a placebo treatment;

[0556] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in a reduction in the frequency of subjects who experience GVHD, compared with a population of subjects that receive no treatment or a placebo treatment.

[0557] In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, a subject having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia is a recipient of a solid organ transplant (SOT). In some embodiments, the SOT is a kidney transplant. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in an increase in the rate of kidney allograft survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia. In some embodiments, the method comprises treating a population of subjects having one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia, the method comprising administering to each subject in the population a composition comprising a polyclonal population of VSTs, said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the method results in an increase in the rate of survival in the population, compared with a population of subjects that receive no treatment or a placebo treatment.

[0558] In some embodiments, a composition described herein comprises cryopreservation medium. In some embodiments, the method comprises thawing a composition comprising cry opreservation medium and administering the composition to a subject within 30 minutes of the completion of the thaw. In some embodiments, the method comprises thawing a composition comprising cry opreservation medium and administering the composition to a subject within 25 minutes of the completion of the thaw. In some embodiments, the method comprises thawing a composition comprising cry opreservation medium and administering the composition to a subject within 20 minutes of the completion of the thaw. In some embodiments, the method comprises thawing a composition comprising cryopreservation medium and administering the composition to a subject within 15 minutes of the completion of the thaw.

Prophylaxis

[0559] In some embodiments, the present disclosure provides methods for preventing or controlling a viral infection or the reactivation of a latent virus via prophylactic administration of a composition comprising a polyclonal population of VSTs. In some embodiments, the compositions comprising polyclonal populations of VSTs are administered as prophylactic treatment. In some embodiments, the composition comprises Posoleucel. In some embodiments, the efficacy of the prophylactic method is measured post-administration of the polyclonal populations of VSTs. In some embodiments, the efficacy of the prophylactic method is measured based on viral load in a sample from the patient. In some embodiments, the efficacy of the prophylactic method is measured by monitoring viral load detectable in the peripheral blood of the patient. In some embodiments, the viral infection is a BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral infection. In some embodiments, the viral infection is a BK viral infection.

[0560] In some embodiments, the present disclosure provides methods for inhibiting a viral infection or the reactivation of a latent virus via administration of a composition comprising a polyclonal population of VSTs to a subject. In some embodiments, a subject is a risk for a viral infection or the reactivation of a latent virus. In some embodiments, the compositions comprising polyclonal populations of VSTs are administered as treatment. In some embodiments, the efficacy of the method is measured post-administration of the polyclonal populations of VSTs. In some embodiments, the efficacy of the method is measured based on viral load in a sample from the patient. In some embodiments, the sample from the patient is as urine sample, a blood sample, a plasma sample, or a peripheral blood sample. In some embodiments, the efficacy of the method is measured by monitoring viral load detectable in urine of the patient. In some embodiments, the efficacy of the method is measured by monitoring viral load detectable in the blood of the patient. In some embodiments, the efficacy of the method is measured by monitoring viral load detectable in the plasma of the patient. In some embodiments, the efficacy of the method is measured by monitoring viral load detectable in the peripheral blood of the patient. In some embodiments, the viral infection is a BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral infection. In some embodiments, the viral infection is a BK viral infection.

[0561] The term “prevent” or “preventing” with regard to a subject refers to keeping a disease or disorder from afflicting the subject or to reducing the severity of a disease or disorder that would otherwise occur in the subject. Prophylactic treatment encompasses preventing. For instance, preventing can include administering to the subject a compound disclosed herein before a subject is afflicted with a disease, is infected with a virus, or undergoes reactivation of a latent virus infection. In some embodiments, preventing means that the administration of the prophylactic treatment will keep the subject from being afflicted with the disease, keep the subject from being infected with the virus, or keep the latent virus from reactivating. Prophylactic treatment also encompasses controlling. For example, controlling a viral infection means that the administration of the prophylactic treatment is prior to the viral infection, wherein the prophylactic treatment controls and/or resolves the subsequent viral infection before it causes significant disease, morbidity or mortality. Controlling a viral infection also means that the administration of the prophylactic treatment is prior to reactivation of a latent virus, and will control and/or resolve the reactivated virus before it causes significant disease, morbidity or mortality. Accordingly, a method provided herein for “controlling” a viral infection means that the viral infection is prevented or readily cleared by a previously administered, prophylactic treatment with the a polyclonal population of VSTs provided herein.

[0562] Without wishing to be bound by any theories, VSTs are capable of circulating for at least 6 weeks or at least 12 weeks and prophylactically prevent viral infection or prophylactically prevent reactivation of a latent virus. In some embodiments, VSTs recognize and kill virus-infected cells via their native T cell receptor (TCR), which binds to major histocompatibility complex (MHC) molecules expressed on target cells that present virus- derived peptides. In some embodiments, the polyclonal population of VSTs circulate for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks when administered prophylactically. In some embodiments, the polyclonal population of VSTs circulate for at least 6 weeks when administered prophylactically. In some embodiments, the polyclonal population of VSTs circulate for at least 12 weeks when administered prophylactically.

[0563] In some embodiments, the polyclonal population of VSTs persist for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks when administered prophylactically. In some embodiments, the polyclonal population of VSTs persist for at least 6 weeks when administered prophylactically. In some embodiments, the polyclonal population of VSTs persist for at least 12 weeks when administered prophylactically.

[0564] In some embodiments, the polyclonal population of VSTs persist for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks after administration to the subject. In some embodiments, the polyclonal population of VSTs persist for more than 15 weeks after administration to the subject. In some embodiments, the polyclonal population of VSTs persist for at least 6 weeks after administration to the subject. In some embodiments, the polyclonal population of VSTs persist for at least 12 weeks after administration to the subject. [0565] In some embodiments, the polyclonal population of VSTs persist for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks after first administration to the subject. In some embodiments, the polyclonal population of VSTs persist for more than 15 weeks after first administration to the subject. In some embodiments, the polyclonal population of VSTs persist for at least 6 weeks after first administration to the subject. In some embodiments, the polyclonal population of VSTs persist for at least 12 weeks after first administration to the subject.

[0566] In some embodiments, a subject does not have viremia or viruria or otherwise detectable virus with respect to a given virus, and is prophylactically administered a composition provided herein, wherein the subject subsequently becomes exposed to and/or infected with and/or reactivates the given virus, and wherein the prophylactic administration of the composition prevents the infection, controls the infection, resolves the infection, and/or prevents serious disease or complications that otherwise result from the infection. In some embodiments, the virus is BKV, CMV, EBV, AdV, JCV, and/or HHV6. In some embodiments, the virus is BK virus.

[0567] In some embodiments, a subject is at risk for viremia or viruria or otherwise detectable virus with respect to a given virus, and is administered a composition provided herein, wherein the subject subsequently becomes exposed to and/or infected with and/or reactivates the given virus, and wherein the administration of the composition inhibits the infection, controls the infection, resolves the infection, and/or inhibits serious disease or complications that otherwise result from the infection. In some embodiments, the virus is BKV, CMV, EBV, AdV, JCV, and/or HHV6. In some embodiments, the virus is BK virus. [0568] In some embodiments, the disclosure provides a method of preventing BKV AN in a subject, the method comprising prophylactically administering a composition provided herein. In some embodiments, the disclosure provides a method of preventing BKV AN in a subject, the method comprising prophylactically administering a composition provided herein, wherein the subject subsequently becomes exposed to and/or infected with and/or reactivates a virus, and wherein the prophylactic administration of the composition prevents the infection, controls the infection, resolves the infection, and/or prevents serious disease or complications that otherwise result from the infection and prevents BKV AN. In some embodiments, the disclosure provides a method of inhibiting BKV AN in a subject at risk for BKV AN, the method comprising administering a composition provided herein. In some embodiments, the disclosure provides a method of inhibiting BKVAN in a subject at risk for BKVAN, the method comprising administering a composition provided herein, wherein the subject subsequently becomes exposed to and/or infected with and/or reactivates a virus, and wherein the administration of the composition inhibits the infection, controls the infection, resolves the infection, and/or inhibits serious disease or complications that otherwise result from the infection and inhibits BKVAN.

Rechallenge

[0569] In some embodiments, a polyclonal population of VSTs prevent reactivation of latent virus. In some embodiments, a polyclonal population of VSTs prevent re-infection of BKV. In some embodiments, a polyclonal population of VSTs prevent re-infection with one of more of CMV, AdV, EBV, BKV, and/or HHV6. In some embodiments, a polyclonal population of VSTs prevent re-infection with one of more of CMV, AdV, EBV, BKV, JCV, and/or HHV6.

[0570] In some embodiments, viral load is controlled below the level of detection by persisting VSTs. In some embodiments, a polyclonal population of VSTs persists after levels of viral load are undetectable. In some embodiments, a polyclonal population of VSTs persist after levels of viral load are undetectable and prevent reactivation of latent virus. In some embodiments, a polyclonal population of VSTs persist after levels of viral load are undetectable and prevent re-infection of BKV. In some embodiments, a polyclonal population of VSTs persist after levels of viral load are undetectable and prevent re-infection with one of more of CMV, AdV, EBV, BKV, and/or HHV6. In some embodiments, a polyclonal population of VSTs persist after levels of viral load are undetectable and prevent re-infection with one of more of CMV, AdV, EBV, BKV, JCV and/or HHV6.

[0571] In some embodiments, the polyclonal population of VSTs persisting after levels of viral load are undetectable for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks, and the persisting VSTs prevent reactivation of latent virus. In some embodiments, the polyclonal population of VSTs persisting after levels of viral load are undetectable for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks, and the persisting VSTs prevent re-infection of BKV. In some embodiments, the polyclonal population of VSTs persisting after levels of viral load are undetectable for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks, and the persisting VSTs prevent re-infection with one of more of CMV, AdV, EBV, BKV, and/or HHV6. . In some embodiments, the polyclonal population of VSTs persisting after levels of viral load are undetectable for at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, or at least 15 weeks, and the persisting VSTs prevent re-infection with one of more of CMV, AdV, EBV, BKV, JCV, and/or HHV6.

Routes of Administration

[0572] In some embodiments, the composition comprising a polyclonal population of VSTs described herein is administered to a subject. In some embodiments, the composition is administered to the subject by intravenous infusion. In some embodiments, the composition is administered to the subject by a peripheral line. In some embodiments, the composition is administered to the subject by a central line. In some embodiments, the composition comprises Posoleucel.

[0573] In some embodiments, the composition is administered by slow push infusion. In some embodiments, the composition is administered over approximately 4, 5 ,6 , 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 4 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 5 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 6 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 7 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 8 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 9 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 10 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 30 minutes by slow push infusion. In some embodiments, the composition is administered over approximately 60 minutes by slow push infusion. Exemplary Embodiments

[0574] In some embodiments, the disclosure provides a method of treating a subject comprising administering a polyclonal population of VSTs. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 3 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 3 weeks followed by administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 14 days for the remainder of a 12-week treatment period. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 3 weeks followed by administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 28 days for the remainder of a 12-week treatment period. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 6 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 7 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 8 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once weekly for 6 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once weekly for 7 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once weekly for 8 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once weekly for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once weekly. [0575] In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once every two weeks for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once every 14 days for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs over 14 weeks on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 7 doses of 4xl0 ⁷ cells of a polyclonal population of VSTs wherein the doses are administered 2 weeks apart.

[0576] In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every two weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every two weeks for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 14 days for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 14 days (± three days) for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 2 weeks for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 14 days for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 14 days (± three days) for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 2 weeks for 7 doses. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 2 weeks for 8 doses. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject every 2 weeks for 7 doses, over 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject in 7 doses wherein the doses are administered on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject on day 1 and then every two weeks thereafter. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject in 7 doses, wherein the doses are administered on day 1 and then every two weeks thereafter. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject in 8 doses, wherein the doses are administered on day 1 and then every two weeks thereafter. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject on day 1, day 15, day 29, day 43, day 57, day 71, and day 85. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject on day 1 (± three days), day 15 (± three days), day 29 (± three days), day 43 (± three days), day 57 (± three days), day 71 (± three days), and day 85 (± three days). In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject on day 1, day 14, day 28, day 42, day 56, day 70, and day 84. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs to the subject on day 1 (± three days), day 14 (± three days), day 28 (± three days), day 42 (± three days), day 56 (± three days), day 70 (± three days), and day 84 (± three days). [0577] In some embodiments, the subject is an adult patient.

[0578] In some embodiments, the subject is a pediatric patient. In some embodiemnnts, a pediatric patient weighs less than 40 Kg. In some embodiments, a pediatic patient is administered half the dose of any of the doses described herein.

[0579] In some embodiments, the disclosure provides a method of treating a subject comprising administering a polyclonal population of VSTs wherein the population of VSTs is administered according to the treatment scheme of Arm 1 in FIG. 3. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs wherein the population of VSTs is administered according to the treatment scheme of Arm 1 in FIG. 3. In some embodiments, the disclosure provides a method of treating a subject comprising administering a polyclonal population of VSTs wherein the population of VSTs is administered over a 12 week period, wherein the first administration is on Day 0, the second administration is at week 1, the third administration is at week 2, the fourth administration is at week 4, the fifth administration is at week 6, the sixth administration is at week 8, the seventh administration is at week 10, and the eight administration is at week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs wherein the population of VSTs is administered over a 12 week period, wherein the first administration is on Day 0, the second administration is at week 1, the third administration is at week 2, the fourth administration is at week 4, the fifth administration is at week 6, the sixth administration is at week 8, the seventh administration is at week 10, and the eight administration is at week 12.

[0580] In some embodiments, the disclosure provides a method of treating a subject comprising administering a polyclonal population of VSTs wherein the population of VSTs is administered according to the treatment scheme of Arm 2 in FIG. 3. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs wherein the population of VSTs is administered according to the treatment scheme of Arm 2 in FIG. 3. In some embodiments, the disclosure provides a method of treating a subject comprising administering a polyclonal population of VSTs wherein the population of VSTs is administered over a 12 week period, wherein the first administration is on Day 0, the second administration is at week 1, the third administration is at week 2, the fourth administration is at week 6, and the fifth administration is at week 10. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs wherein the population of VSTs is administered over a 12 week period, wherein the first administration is on Day 0, the second administration is at week 1, the third administration is at week 2, the fourth administration is at week 6, and the fifth administration is at week 10.

[0581] In some embodiments, the disclosure provides a method of treating a subject comprising administering Posoleucel. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel every 7 days for 3 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel every 7 days for 3 weeks followed by administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 14 days for the remainder of a 12-week treatment period. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 7 days for 3 weeks followed by administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 28 days for the remainder of a 12-week treatment period. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel every 7 days for 6 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ Posoleucel cells every 7 days for 7 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel every 7 days for 8 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel every 7 days for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel every 7 days. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel once weekly for 3 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel once weekly for 3 weeks followed by administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 14 days for the remainder of a 12-week treatment period. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a polyclonal population of VSTs once weekly for 3 weeks followed by administering 4xl0 ⁷ cells of a polyclonal population of VSTs every 28 days for the remainder of a 12-week treatment period. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel once weekly for 6 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel once weekly for 7 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel once weekly for 8 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel once weekly for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of a Posoleucel once weekly.

[0582] In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel once every two weeks for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel once every 14 days for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel over 14 weeks on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 7 doses of 4xl0 ⁷ cells of Posoleucel wherein the doses are administered 2 weeks apart.

[0583] In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every two weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every two weeks for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 14 days for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 14 days (± three days) for 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 2 weeks for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 14 days for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 14 days (± three days) for 14 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 2 weeks for 7 doses. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 2 weeks for 8 doses. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject every 2 weeks for 7 doses, over 12 weeks. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject in 7 doses wherein the doses are administered on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject on day 1, week 2, week 4, week 6, week 8, week 10, and week 12. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject on day 1 and then every two weeks thereafter. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject in 7 doses, wherein the doses are administered on day 1 and then every two weeks thereafter. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject in 8 doses, wherein the doses are administered on day 1 and then every two weeks thereafter. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject on day 1, day 15, day 29, day 43, day 57, day 71, and day 85. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject on day 1 (± three days), day 15 (± three days), day 29 (± three days), day 43 (± three days), day 57 (± three days), day 71 (± three days), and day 85 (± three days). In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject on day 1, day 14, day 28, day 42, day 56, day 70, and day 84. In some embodiments, the disclosure provides a method of treating a subject comprising administering 4xl0 ⁷ cells of Posoleucel to the subject on day 1 (± three days), day 14 (± three days), day 28 (± three days), day 42 (± three days), day 56 (± three days), day 70 (± three days), and day 84 (± three days).

[0584] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0585] In some embodiments, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0586] In some embodiments, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, thereby treating or preventing BK viremia in the subject.

[0587] In some embodiments, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0588] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, thereby treating BK viremia in the subject.

[0589] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, thereby treating BK viremia in the subject.

[0590] In some embodiments, the disclosure provides A method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the

\T1 composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0591] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0592] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0593] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0594] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), thereby treating BK viremia in the subject.

[0595] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0596] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0597] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), thereby treating BK viremia in the subject.

[0598] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0599] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0600] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0601] In some embodiments, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0602] In some embodiments, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject.

[0603] In some embodiments, the disclosure provides a method for treating or preventing BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing BK viremia in the subject. [0604] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0605] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0606] In some embodiments, the disclosure provides A method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0607] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0608] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject. [0609] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0610] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0611] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0612] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0613] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0614] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0615] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject. In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for seven weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0616] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for seven weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject. [0617] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for seven weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0618] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for seven weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0619] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for seven weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0620] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for seven weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject. [0621] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0622] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0623] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every 14 days (± three days) for 12 weeks, followed and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0624] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0625] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject. [0626] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0627] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0628] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0629] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject on day 1 and every 14 days (± three days) thereafter for 12 weeks, followed and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0630] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject on day 1 and every 14 days (± three days) thereafter for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0631] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject on day 1 and every 14 days (± three days) thereafter for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0632] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject on day 1 and every 14 days (± three days) thereafter for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0633] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject on day 1 and every 14 days (± three days) thereafter for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject. [0634] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject on day 1 and every 14 days (± three days) thereafter for 12 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0635] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every 14 days (± three days) for 14 weeks, followed and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0636] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every 14 days (± three days) for 14 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0637] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every 14 days (± three days) for 14 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0638] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 14 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0639] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 14 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0640] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 14 weeks, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0641] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every 14 days (± three days) for 7 doses, followed and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0642] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every 14 days (± three days) for 7 doses, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0643] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every 14 days (± three days) for 7 doses, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating BK viremia in the subject.

[0644] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 7 doses, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0645] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 7 doses, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0646] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every 14 days (± three days) for 7 doses, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0647] In some embodiments, the subject is the recipient of a solid organ transplant. In some embodiments, the solid organ transplant is a kidney transplant. In some embodiments, the solid organ transplant is a heart transplant. In some embodiments, the solid organ transplant is a lung transplant. In some embodiments, the solid organ transplant is a liver transplant. In some embodiments, the solid organ transplant is an intestine transplant. In some embodiments, the solid organ transplant is a pancreas transplant.

[0648] In some embodiments, the subject received a solid organ transplant about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 12 months, about 18 months or about 24 months prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 week prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 1 week prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 2 weeks prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 1 month prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 5 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 4 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 3 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 2 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 18 months prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 1 year prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month to about 6 months prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 5 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 4 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 3 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 2 years prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 18 months prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 1 year prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 day to about 6 months prior to administration of a composition described herein. In some embodiments, the subject received a solid organ transplant about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years about 2 years, about 2.5 years, about 3 years, about 3.5 years, about 4 years, about 4.5 years, or about 5 years prior to administration of a composition described herein. In some embodiments, a subject received a solid organ transplant less than 2 years prior to administration of a composition described herein. In some embodiments, a subject received a solid organ transplant less than 1 year prior to administration of a composition described herein. In some embodiments, a subject received a solid organ transplant less than 6 months prior to administration of a composition described herein.

[0649] In some embodiments, the subject received a kidney transplant about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 12 months, about 18 months, or about 24 months prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 week prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 1 week prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 2 weeks prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 1 month prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 5 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 4 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 3 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 2 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 18 months prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 1 year prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month to about 6 months prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 5 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 4 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 3 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 2 years prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 18 months prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 1 year prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 day to about 6 months prior to administration of a composition described herein. In some embodiments, the subject received a kidney transplant about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 1.5 years about 2 years, about 2.5 years, about 3 years, about 3.5 years, about 4 years, about 4.5 years, or about 5 years prior to administration of a composition described herein. In some embodiments, a subject received a kidney transplant less than 2 years prior to administration of a composition described herein. In some embodiments, a subject received a kidney transplant less than 1 year prior to administration of a composition described herein. In some embodiments, a subject received a kidney transplant less than 6 months prior to administration of a composition described herein.

[0650] In some embodiments, the disclosure provides a method for treating BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% relative to baseline viral load.

[0651] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 50% relative to baseline viral load.

[0652] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 60% relative to baseline viral load.

[0653] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 70% relative to baseline viral load.

[0654] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 80% relative to baseline viral load.

[0655] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 90% relative to baseline viral load.

[0656] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 95% relative to baseline viral load.

[0657] In some embodiments, the disclosure provides a method for treating BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% relative to baseline viral load.

[0658] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 50% relative to baseline viral load.

[0659] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 60% relative to baseline viral load. [0660] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 70% relative to baseline viral load.

[0661] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 80% relative to baseline viral load.

[0662] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 90% relative to baseline viral load.

[0002] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 95% relative to baseline viral load.

[0663] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by >1 logio copies/mL relative to baseline viral load.

[0664] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by >1 logio copies/mL relative to baseline viral load.

[0665] In some embodiments, the disclosure provides a method for reducing BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject in need thereof, comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% relative to baseline viral load.

[0666] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 50% relative to baseline viral load.

[0667] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 60% relative to baseline viral load.

[0668] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 70% relative to baseline viral load.

[0669] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 80% relative to baseline viral load.

[0670] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 90% relative to baseline viral load.

[0671] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by at least 95% relative to baseline viral load.

[0672] In some embodiments, the disclosure provides a method for reducing BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BKV, CMV, EBV, AdV, JCV, and/or HHV6 viral load by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% relative to baseline viral load.

[0673] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 50% relative to baseline viral load.

[0674] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 60% relative to baseline viral load. [0675] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 70% relative to baseline viral load.

[0676] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 80% relative to baseline viral load.

[0677] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 90% relative to baseline viral load.

[0678] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by at least 95% relative to baseline viral load.

[0679] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein administration reduces BK viral load by >1 logio copies/mL relative to baseline viral load.

[0680] In some embodiments, the disclosure provides a method for reducing BK viral load in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein administration reduces BK viral load by >1 logio copies/mL relative to baseline viral load.

[0681] In some embodiments, the viral load is plasma viral load. In some embodiments, the viral load is serum viral load.

[0682] In some embodiments, the disclosure provides a method for treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0683] In some embodiments, the disclosure provides a method for treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with cross-reactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, thereby treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0684] In some embodiments, the disclosure provides a method for treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus, (with cross-reactivity for JCV) wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0685] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0686] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0687] In some embodiments, the disclosure provides A method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0688] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject. [0689] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0690] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject. [0691] In some embodiments, the disclosure provides a method for treating one or more of CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0692] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0693] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject. [0694] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0695] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0696] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from one or more of BKV, CMV, EBV, AdV, and/or HHV6 virus (with crossreactivity for JCV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject. [0697] In some embodiments, the disclosure provides a method for treating or preventing viral infection or disease in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, said population comprising specificity for at least one antigen from cytomegalovirus (CMV), Adenovirus (AdV), Epstein-Barr virus (EBV), BK virus (BKV) and/or human herpes virus 6 (HHV-6), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing viral infection or disease in the subject.

[0698] In some embodiments, the disclosure provides a method for treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0699] In some embodiments, the disclosure provides a method for treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0700] In some embodiments, the disclosure provides a method for treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating or preventing one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0701] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0702] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0703] In some embodiments, the disclosure provides A method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0704] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0705] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0706] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the patient every 7 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0707] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0708] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0709] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0710] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ cells (i.e., Posoleucel) to about 1.6xl0 ⁸ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0711] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ cells (i.e., Posoleucel) to about 8xl0 ⁷ cells (i.e., Posoleucel), wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

[0712] In some embodiments, the disclosure provides a method for treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ cells (i.e., Posoleucel), and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days), and wherein the subject is the recipient of a solid organ transplant (SOT), thereby treating one or more of BKV, CMV, EBV, AdV, JCV, and/or HHV6 viremia in the subject.

Methods of Use

[0713] In some embodiments, the disclosure provides a composition comprising a polyclonal population of VSTs for use in treating BK viremia. In some embodiments, the disclosure provides a composition comprising a Posoleucel for use in treating BK viremia.

[0714] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs.

[0715] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs.

[0716] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs.

[0717] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 7 days (± three days). [0718] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 7 days (± three days) for 7 weeks.

[0719] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 14 weeks.

[0720] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 12 weeks.

[0721] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 14 days (± three days) for 12 weeks.

[0722] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter.

[0723] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter for 12 weeks.

[0724] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 14 days (± three days).

[0725] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 2 weeks for seven doses, over 12 weeks.

[0726] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days), thereby treating BK viremia in the subject.

[0727] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days) for seven weeks, thereby treating BK viremia in the subject.

[0728] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient 14 days (± three days) for 14 weeks, thereby treating BK viremia in the subject.

[0729] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 12 weeks.

[0730] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter.

[0731] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter for 12 weeks.

[0732] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days).

[0733] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 2 weeks for seven doses, over 12 weeks.

[0734] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days). In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days) for seven weeks.

[0735] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 14 weeks.

[0736] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 12 weeks.

[0737] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter.

[0738] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter for 12 weeks.

[0739] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days).

[0740] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 2 weeks for seven doses, over 12 weeks.

[0741] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days).

[0742] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days).

[0743] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days).

[0744] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days).

[0745] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days).

[0746] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days).

[0747] In some embodiments, the subject is a solid organ transplant recipient. In some embodiments, the subject is a kidney transplant recipient. [0748] In some embodiments, the disclosure provides a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) for use in treating or preventing BK virus-associated nephropathy in a subject in need thereof. In some embodiments, the disclosure provides a composition comprising a polyclonal population of virus-specific T lymphocytes (VSTs) for use in treating or preventing BK virus-associated nephropathy in a subject in need thereof, wherein the subject is the recipient of a solid organ transplant.

[0749] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs.

[0750] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, and wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs.

[0751] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, and wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs.

[0752] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 7 days (± three days). [0753] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 7 days (± three days) for 7 weeks.

[0754] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 14 weeks.

[0755] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 12 weeks.

[0756] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 14 days (± three days) for 12 weeks.

[0757] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter.

[0758] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter for 12 weeks.

[0759] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 14 days (± three days).

[0760] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the patient every 2 weeks for seven doses, over 12 weeks.

[0761] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days), thereby treating BK viremia in the subject. [0762] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days) for seven weeks, thereby treating BK viremia in the subject.

[0763] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient 14 days (± three days) for 14 weeks, thereby treating BK viremia in the subject.

[0764] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 12 weeks.

[0765] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter.

[0766] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter for 12 weeks.

[0767] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days).

[0768] In some embodiments, the disclosure provides a method for treating BK viremia in a subject in need thereof, the method comprising administering to the subject a composition comprising Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 2 weeks for seven doses, over 12 weeks.

[0769] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days). In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 7 days (± three days) for seven weeks. [0770] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 14 weeks.

[0771] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days) for 12 weeks. [0772] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter. [0773] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient on day 1 and then every 2 weeks thereafter for 12 weeks.

[0774] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 14 days (± three days). [0775] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the patient every 2 weeks for seven doses, over 12 weeks. [0776] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days). [0777] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days). [0778] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days).

[0779] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days). [0780] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days). [0781] In some embodiments, the disclosure provides a composition for use in treating BK viremia in a subject in need thereof, wherein the composition comprises Posoleucel, wherein the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs, and wherein the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days).

[0782] In some embodiments, the subject is a solid organ transplant recipient. In some embodiments, the subject is a kidney transplant recipient.

[0783] In some embodiments, the disclosure provides a composition comprising Posoleucel for use in treating or preventing BK virus-associated nephropathy in a subject in need thereof. In some embodiments, the disclosure provides a composition comprising Posoleucel for use in treating or preventing BK virus-associated nephropathy in a subject in need thereof, wherein the subject is the recipient of a solid organ transplant.

Pharmaceutical Compositions

[0784] In some embodiments, the disclosure provides pharmaceutical compositions comprising a composition described herein wherein the composition comprises a polyclonal population of VSTs. In some embodiments, the pharmaceutical composition comprises Posoleucel. In some embodiments, the pharmaceutical composition is formulated for intravenous delivery. In some embodiments, the pharmaceutical composition is formulated for intravenous infusion. In some embodiments, the pharmaceutical composition is formulated for administration by a peripheral line. In some embodiments, the pharmaceutical composition is formulated for administration by a central line.

[0785] The present disclosure provides pharmaceutical compositions comprising any compositions formulated for intravenous delivery. In some embodiments, the compositions are negative for bacteria for at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8 days, at least 9 days, at least 10 days, in culture. In some embodiments, the compositions are negative for bacteria for at least 7 days in culture. In some embodiments, the compositions are negative for fungi for at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8 days, at least 9 days, at least 10 days, in culture. In some embodiments, the compositions are negative for fungi for at least 7 days in culture.

[0786] The present pharmaceutical compositions exhibit less than 1 EU/ml, less than 2 EU/ml, less than 3 EU/ml, less than 4 EU/ml, less than 5 EU/ml, less than 6 EU/ml, less than 7 EU/ml, less than 8 EU/ml, less than 9 EU/ml, less than 10 EU/ml of endotoxin. In some embodiments, the present pharmaceutical compositions are negative for mycoplasma. [0787] In some embodiments, the composition comprises a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier is cryopreservation media. In some embodiments, the pharmaceutically acceptable carrier is formulated for intravenous administration. In some embodiments, the pharmaceutically acceptable carrier is formulated for administration by a peripheral line. In some embodiments, the pharmaceutically acceptable carrier is formulated for administration by a central line. Appropriate pharmaceutically acceptable carriers will be known to those of skill in the art.

Kits

[0788] In some embodiments, a composition described herein (e.g. comprising a polyclonal population of VSTs), is provided in a vial comprising about 1.0 x 10 ⁷ cells/mL in a volume of about 2.5 mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁶ cells/mL, 5.0 x 10 ⁶ cells/mL, 1.0 x 10 ⁷ cells/mL, 2.0 x 10 ⁷ cells/mL 5.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁸ cells/mL, or 5.0 x 10 ⁸ cells/mL in 2.5mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁶ cells/mL, 5.0 x 10 ⁶ cells/mL, 1.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁷ cells/mL, 5.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁸ cells/mL, or 5.0 x 10 ⁸ cells/mL in 2.0mL. In some embodiments, the composition is provided in a vial comprising about 2.0 x 10 ⁷ cells/mL in 2.0 mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁶ cells/mL, 5.0 x 10 ⁶ cells/mL, 1.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁷ cells/mL, 5.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁸ cells/mL, or 5.0 x 10 ⁸ cells/mL in 4.0mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁷ cells/mL in 4.0 mL.

[0789] In some embodiments, a composition described herein (e.g. comprising a polyclonal population of VSTs), is provided in a vial comprising about 1.0 x 10 ⁷ cells/mL per 2.5 mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁶ cells/mL, 5.0 x 10 ⁶ cells/mL, 1.0 x 10 ⁷ cells/mL, 2.0 x 10 ⁷ cells/mL 5.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁸ cells/mL, or 5.0 x 10 ⁸ cells/mL per 2.5mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁶ cells/mL, 5.0 x 10 ⁶ cells/mL, 1.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁷ cells/mL, 5.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁸ cells/mL, or 5.0 x 10 ⁸ cells/mL per 2.0mL. In some embodiments, the composition is provided in a vial comprising about 2.0 x 10 ⁷ cells/mL per 2.0 mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁶ cells/mL, 5.0 x 10 ⁶ cells/mL, 1.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁷ cells/mL, 5.0 x 10 ⁷ cells/mL, 1.0 x 10 ⁸ cells/mL, or 5.0 x 10 ⁸ cells/mL per 4.0mL. In some embodiments, the composition is provided in a vial comprising about 1.0 x 10 ⁷ cells/mL per 4.0 mL.

[0790] In some embodiments, the composition comprises a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier is cryopreservation media.

[0791] In some embodiments, the composition comprises cryopreservation media. In some embodiments, the cry opreservation media comprises human serum albumin, Hank’s balance salt solution (HBSS), and dimethyl sulfoxide (DMSO). In some embodiments, the cry opreservation media comprises 25% human serum albumin, Hank’s balance salt solution (HBSS), and dimethyl sulfoxide (DMSO). In some embodiments, the cry opreservation media comprises human serum albumin. In some embodiments, the cryopreservation media comprises Hank’s balance salt solution (HBSS). In some embodiments, the cryopreservation media comprises and dimethyl sulfoxide (DMSO).

[0792] In some embodiments, the disclosure provides a kit comprising a polyclonal population of VSTs herein, or a composition thereof, described herein, and instructions for use. In some embodiments, the kit comprises a polyclonal population of VSTs herein, or a composition thereof, described herein, and a package insert containing instructions for use of the kit and/or any component thereof. In some embodiments, the kit comprises, in a suitable container, a polyclonal population of VSTs herein, or a composition thereof, described herein, one or more controls, and various buffers, reagents, enzymes and other standard ingredients well known in the art. In some embodiments, the container comprises at least one vial, well, test tube, flask, bottle, syringe, or other container means, into which the polyclonal population of VSTs herein, or a composition thereof, is placed, and in some instances, suitably aliquoted. In some embodiments where an additional component is provided, the kit contains additional containers into which this component is placed. The kits can also include a means for containing a polyclonal population of VSTs herein, or a composition thereof, and any other reagent in close confinement for commercial sale. Such containers may include injection or blow-molded plastic containers into which the desired vials are retained. Containers and/or kits can include labeling with instructions for use and/or warnings.

[0793] In some embodiments, the kit comprises a population of VSTs comprising specificity for at least one antigen from one or more of BKV, CMV, AdV, EBV, and/or HHV6. [0794] In some embodiments, the kit comprises a population of VSTs comprising specificity for at least one antigen selected from: i) BK virus antigens VP1 and Large T; ii) AdV antigens Hexon and Penton; iii) CMV antigens IE1 and pp65; iv)EBV antigens LMP2, EBNA1, and BZLF1; and, v) HHV6 antigens U90, U11, and U14.

[0795] In some embodiments, a kit comprises a polyclonal population of VSTs herein, or a composition thereof, described herein, and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising a polyclonal population of VSTs and instructions for treating or delaying progression of a disease, disorder or condition associated with BK viremia in a subject in need thereof.

[0796] In some embodiments, a kit comprises a polyclonal population of VSTs herein, or a composition thereof, described herein, and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising the polyclonal population of VSTs and instructions for treating or delaying progression of a disease, disorder or condition associated with BK viremia in a subject in need thereof.

[0797] In some embodiments, a kit comprises a polyclonal population of VSTs herein, or a composition thereof, described herein, and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising the polyclonal population of VSTs and instructions for treating or delaying progression of a disease, disorder or condition associated with BK virus infection in a subject in need thereof.

[0798] In some embodiments, a kit comprises a polyclonal population of VSTs herein, or a composition thereof, described herein, and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising the polyclonal population of VSTs and instructions for treating or delaying progression of a disease, disorder or condition associated with BK virus infection in a subject in need thereof.

[0799] In some embodiments, a kit comprises a pharmaceutical composition comprising: a polyclonal population of virus-specific T lymphocytes (VSTs), said population comprising specificity for at least one antigen from BK virus (BKV), and a pharmaceutically acceptable carrier, and instructions for treating or preventing BK viremia in a human subject, wherein treatment comprises administration of the pharmaceutical composition by intravenous administration at a dose of about IxlO ⁶ VSTs to about 1.6xl0 ⁸ VSTs. In some embodiments, the subject is a recipient of a solid organ transplant. In some embodiments, the solid organ transplant is a kidney transplant. In some embodiments, the composition is administered to the subject at a dose of about IxlO ⁷ VSTs to about 8xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject at a dose of about 4xl0 ⁷ VSTs. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 14 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for three weeks, followed by administration to the subject every 28 days (± three days) for nine weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 6 weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 7 weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 8 weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 6 weeks. In some embodiments, the composition is administered to the subject every seven days (± three days) for 7 weeks. In some embodiments, the composition is administered to the subject every 14 days (± three days) for 14 weeks. In some embodiments, the composition is administered to the subject every 14 days (± three days) for 12 weeks. In some embodiments, the composition is administered to the subject on day 1 and then every 2 weeks thereafter. In some embodiments, the composition is administered to the subject on day 1 and then every 2 weeks thereafter for 12 weeks. In some embodiments, the composition is administered to the subject every 14 days (± three days). In some embodiments, the composition is administered to the subject every 2 weeks for seven doses, over 12 weeks. [0800] In some embodiments, the composition is administered to the subject every seven days (± three days) for 12 weeks. In some embodiments, the composition is administered to the subject weekly. In some embodiments, the composition is Posoleucel. In some embodiments, the pharmaceutically acceptable carrier is cry opreservation media.

EXAMPLES Example 1. Generation of Posoleucel, a Multi-Virus Specific T-cell Therapy (VST)

BK viremia is detected in 10-20% of kidney transplant recipients. 70% of patients will have BK viremia in year 1 after transplant surgery; 95% will have BK viremia by year 2. Prior to the discovery of the present disclosure, there were no effective antiviral therapies for BK virus.

Patients in the treatment arms of the following study received Posoleucel (also referred to herein as PSL, ALVR105, and Viralym-M). Posoleucel is a third-party, donor- derived, “off-the-shelf,” multi-virus specific T cell product with specificity for BKV, AdV, CMV, EBV, and HHV-6 (with additional cross-reactive specificity for JCV) that is cryopreserved and ready for immediate use. The placebo arm of the following study will receive separate IV infusions of cry opreservation media (without cells) as placebo.

The Posoleucel manufacturing process was performed as previously described by the inventors in US2018/0187152, WO2013/119947 and Tzannou et al., J Clin Oncol. 2017 Nov 1; 35(31 : 3547-3557, each of which is incorporated herein by reference in its entirety.

An exemplary scheme for the manufacture of Posoleucel (PSL) is shown in FIG. 1. PBMCs from healthy, seropositive, transplant donor-eligible volunteers were directly stimulated with pepmixes spanning each of BKV VP1 and BKV large T, AdV hexon and AdV penton, CMV IE1 and CMV pp65, EBV LMP2, EBV EBNA1, and EBV BZLF1, and HHV-6 U90, HHV-6 U11, and HHV-6 U14, and cultured in medium supplemented with the growth-promoting cytokines IL-4 and IL-7 to promote the expansion of multivirus-specific T cells. Twelve-pepmixes each spanning of the viral antigens used in the initial stimulation are used as a stimulus in an interferon (IFN)-y ELIspot assay to measure the potency of PSL cell lines. Only those cell lines reaching pre-specified minimum potency criteria were released for clinical use. The percentage of CD3+, CD4+, and CD8+ cells was also measured for the cell lines (FIG. 2) demonstrating the phenotype and polyclonality of Posoleucel. PSL cell lines were checked for virus specificity, cell concentration, viability, identity, phenotype, potency, endotoxin, mycoplasma, and sterility per the study requirements (data not shown) and then cryopreserved and stored for use in the study.

Example 2. Study Design and Patient Characteristics

A Phase 2 multicenter, randomized, double-blind, placebo-controlled, multiple dosing interval, 2-period study (NCT04605484 on clinicaltrials.gov, incorporated herein by reference in its entirety) was conducted to assess the safety, tolerability, and effectiveness of adoptively transferred Posoleucel (also referred to herein as PSL, ALVR105, and Viralym- M) multivirus-specific T cells in kidney transplant recipients with either high or low levels of BK viremia.

The primary objective of the study was to assess the safety and tolerability of Posoleucel compared to placebo in kidney transplant patients with BK viremia. In some embodiments, the primary objective was assessed by treatment-emergent adverse events (TEAEs), changes in vital signs, physical exams, laboratory assessments, and electrocardiograms (ECGs). During the 24 week study, patients were monitored for adverse events following each infusion and during the dosing period.

A secondary objective of the study was to assess the overall efficacy of Posoleucel to suppress BK viral load compared to placebo in kidney transplant recipients. In some embodiments, the secondary objective was assessed by measuring changes in BK viremia in patients receiving Posoleucel compared to patients receiving placebo. Changes in BK viral load were measured based on quantitation of mean +/- standard deviation of BK viral load as determined by BK viral load assay (e.g., quantitative polymerase chain reaction (qPCR) assay). Additional secondary objectives included comparing the relative efficacy of different dosing regimens of Posoleucel to suppress BK viral load compared to placebo. In some embodiments, changes in BK viremia in patients receiving different dosing regimens of Posoleucel were compared with changes in BK viremia in patients receiving placebo.

The present study was comprised of two periods. Period 1 included a 2-week window for screening assessments following by a 12-week treatment period for eligible patients. Period 2 included a 12-week follow-up period. Overall, the total duration of patient participation in the study was approximately 26 weeks (2 weeks for screening, 12 weeks for treatment, and 12 weeks of follow-up).

Patients were stratified by BK plasma viral load. One stratum consisted of patients with a

BK viral load 350 to <10,000 copies/mL, and the other stratum consisted of patients with a BK viral load >10,000 to 10,000,000 copies/mL.

Study participants were male and female patients age 18 years or older who, prior to Period 1 (dosing period), were screened for inclusion in the study. Inclusion criteria included:

(1) a kidney transplant performed greater than or equal to 28 days prior to enrollment;

(2) were diagnosed with BK viremia based on the following criteria: (a) any positive whole blood or plasma BK viral load at a local laboratory obtained less than or equal to 90 days before the start of screening, and

(b) confirmation of BK viremia of 350 copies/mL - 10,000,000 copies/mL as determined by the central laboratory screening; and

(3) at least one identified, suitably matched Posoleucel (ALVR105) cell line for infusion was available.

Exclusion criteria include the following:

Patients were excluded from the study if the patient had (1) undergone allogeneic hematopoietic cell transplantation, (2) demonstrated evidence or history of graft versus host disease (GVHD) or cytokine release syndrome (CRS), (3) uncontrolled or progressive bacterial or fungal infections, (4) uncontrolled or progressive viral infections not targeted by PSL, (5) uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder, (6) known or presumed pneumonia, (7) hemodynamic or respiratory instability, (8) evidence of any medical condition that in the opinion of the Investigator might interfere with the patient’s ability to participate in the trial, (9) ongoing therapy with high-dose systemic corticosteroids (for example, prednisone dose >0.5 mg/kg/day or equivalent), (10) received, or are planned to receive, abatacept or belatacept, within 3 months of screening, or who received equine anti-thymocyte globulin ([ATG] Atgam®) or rabbit ATG (Thymoglobulin ®) in doses of >4.5 mg/kg or alemtuzumab (Campath-IH) or other immunosuppressive T cell-targeted monoclonal antibodies <28 days prior to randomization, (11) received other investigational antiviral treatments within 28 days or 5 half-lives (whichever is longer) prior to randomization, (12) Pregnant or nursing or planning to become pregnant, (13) ABO incompatible or complement-dependent lymphocytotoxic crossmatch positive transplant (isolated positive B cell crossmatches are not an exclusion criterion), (14) weight <40 kg, (15) history of hypersensitivity to any of the components of the investigational product, (16) liver dysfunction, defined as liver transaminases (ie, aspartate aminotransferase or alanine aminotransferase) >5 times the upper limit of normal (ULN) or direct bilirubin >2 times the ULN reference per local laboratory, and/or (17) renal dysfunction, defined as estimated glomerular filtration rate (eGFR) (estimated by Modified Dose in Renal Disease [MDRD] formula) <20 mL/min/1.73 m2.

Posoleucel cell lines were selected for each patient based on an overall HLA match between the VST line and transplanted organ, with 2 alleles set as a minimum threshold, as well as the HLA match between the VST line and the patient, with 1 allele set as a minimum threshold. The HLA alleles used for evaluation of matching were HLA-A, HLA-B, HLA-DR, and HLA-DQ.

The appropriate study treatment (i.e., the cell lines for infusion) for patient administration was selected using a modification of the software program (CytoMatch), which used a stepwise algorithm to identify the best overall HLA-matched Posoleucel study treatment lots for each patient. The HLA types of the patient and of their donor kidney (obtained from the medical record) were manually entered into the software and verified before the cell matching algorithm was run. CytoMatch compares each Posoleucel study treatment lot available in the bank first with the HLA type of the donor kidney, and second with that of the patient, and generates an overall total score that was used to establish a ranking hierarchy of matching cell lines. To be suitable for infusion, a cell line must be matched at 2 or more HLA alleles to the virus-infected recipient’s allograft and at least 1 HLA allele of the patient. The top ranked Posoleucel study treatment lots were identified by CytoMatch as the cell lines with the highest overall HLA match total. In the event of a tie, the selection process followed the First in/First out method. A schematic of the matching process for transplant and patient HLA matching is provided in FIG. 3.

Randomization of patients to Posoleucel versus placebo occurred after cell line matching and selection was confirmed, to satisfy inclusion criteria. Premedication was not required, except for patients with a prior history of reaction to blood products. These patients received premedication with 0.25 to 0.5 mg/kg (maximum dose of 25 mg) diphenhydramine (IV or oral) and/or 5 to 10 mg/kg (maximum dose of 650 mg) acetaminophen (IV or oral) prior to study treatment administration. Premedication with corticosteroids was prohibited in the study.

Following randomization, patients were monitored for safety, BK viral load, renal function, and immune function, including modification of immunosuppression reduction.

Patients received infusions of either Posoleucel (PSL) or placebo for 12 weeks. Cry opreservation media (without cells) served as the placebo and was identical in volume and appearance upon administration. All infusions were administered intravenously (IV) (via peripheral or central line) over approximately 5 minutes as a slow push. Patients received the same dose for all infusions. The study consisted of three treatment arms. To maintain the blind, all patients received an infusion (either PSL or placebo) weekly for the first 3 weeks of the dosing period, followed by biweekly (every other week) dosing for the remaining 9 weeks. The treatment arms and associated infusions were as follows:

• Arm 1 (Regimen A - Posoleucel): Posoleucel (4* 10 ⁷ cells) was administered every 7 days (±3 days) for 3 weeks, followed by Posoleucel (4* 10 ⁷ cells) administered every 14 days (±3 days) for the remainder of the 12-week dosing period. In some embodiments, Arm 1 is referred to as the “active” protocol.

• Arm 2 (Regimen B - Posoleucel and Placebo): Posoleucel (4* 10 ⁷ cells) was administered every 7 days (±3 days) for 3 weeks, followed by Posoleucel (4* 10 ⁷ cells) administered every 28 days (±3 days) for the remainder of the 12-week dosing period. Placebo was administered 14 days (±3 days) after the 3rd infusion, and then every 28 days (±3 days) for the remainder of the 12-week dosing period. In some embodiments, Arm 2 is referred to as the “hybrid” protocol.

• Arm 3 (Placebo): Placebo was administered every 7 days (±3 days) for 3 weeks, followed by placebo administered every 14 days (±3 days) for the remainder of the 12-week dosing period.

A schematic of the study design is provided in FIG. 4.

After the first three doses, patients who had undetectable BK plasma viral load at 2 or more consecutive assessments at least 2 weeks apart discontinued PSL infusions. If a patient’s viral load became undetectable, the patient was followed every 14 days for study evaluations. No patients were permitted to receive a subsequent infusion of PSL/placebo if they developed new onset graft versus host disease (GVHD) (>Stage 1) or cytokine release syndrome (CRS >Grade 2) at the proposed time for infusion of any subsequent dose.

During Period 1 (weeks -2 to 12), patients were monitored and assessed at study day - 14 to -1, day 1, day 8 (± 2 days), day 15 (± 3 days), day 29 (± 3 days), day 43 (± 3 days), day 57 (± 3 days), day 71 (± 3 days), and day 85 (± 3 days) for (1) prior and concurrent medications, (2) adverse events, (3) a targeted or complete physical examination was conducted, (4) vital signs were monitored, and (5) any clinically indicated kidney biopsy pathological specimens were obtained for review. In addition, at study day -14 to -1, day 1, day 15 (± 3 days), day 29 (± 3 days), day 43 (± 3 days), day 57 (± 3 days), day 71 (± 3 days), and day 85 (± 3 days) (1) clinical labs were performed, and (2) BKV plasma viral load was assayed. At day 1, day 29 (± 3 days), day 57 (± 3 days), and day 85 (± 3 days) AdV, CMV, JCV, EBV, and HHV-6 plasma viral load was assayed. At study day -14 to -1, day 1, day 29 (± 3 days), day 57 (± 3 days), and day 85 (± 3 days) patients height and weight were measured. At study day -14 to -1, day 15 (± 3 days), day 29 (± 3 days), day 43 (± 3 days), day 57 (± 3 days), and day 85 (± 3 days) PBMCs were banked for virus-specific immunity. At study day -14 to -1, day 1, and day 15 (± 3 days) 12-lead ECG was analyzed. Blood for donor DNA was analyzed at study day 29 (± 3 days) and day 85 (± 3 days) and donor-specific antibodies were analyzed at study day 1 and day 85 (± 3 days).

During Period 2 (weeks 14-24; the follow-up period), patients were monitored and assessed at day 99 ± 7 days, day 113 ± 7 days, day 127 ± 7 days, day 141 ± 7 days, day 155 ± 7 days, and day 169 ± 7 days for (1) prior and concurrent medications, (2) adverse events, (3) a targeted physical examination was conducted, (4) vital signs were monitored, (5) BKV plasma viral load was assayed, and (6) any clinically indicated kidney biopsy pathological specimens were obtained for review. In addition, at days 113 ± 7 days, day 141 ± 7 days, and day 169 ± 7 days patients were (1) weighed, (2) clinical labs were performed, (3) AdV, CMV, JCV, EBV, and HHV-6 plasma viral load was assayed, and (4) PBMCs were banked for virus-specific immunity. At day 169 ± 7 days 12-lead ECG was analyzed, blood for donor DNA was analyzed, and donor-specific antibodies were analyzed.

Example 3: Patients Treated with Posoleucel Demonstrated Posoleucel VST Persistence In Vivo Through 24 Weeks

Without being bound by theory, it is believed that persistence of virus-specific T-cell (VST) lines in a patient results in sustained protection from the viruses that are targeted by the VSTs. In the present study, Posoleucel VST persistence was observed in patient’s treated with Posoleucel during the infusion period and up to at least 12 weeks after the last infusion.

Patients were treated with Posoleucel as described in Example 2. During the infusion period and up to 12 weeks after the last infusion, samples of blood were taken from patients to assay for Posoleucel VST persistence. For interim analyses, samples from four patients were evaluated at weeks 0, 4, and 12 and samples from three patients were evaluated at weeks 0, 4, 12, and 24(FIG. 5). The samples were processed to generate a PBMC fraction and a plasma fraction. The PBMCs (peripheral blood mononuclear cells) collected from patients were subjected to deep sequencing of TCRvP using ImmunoSEQ® following the manufacture’s recommendations. Deep sequencing of TCRvP allowed for the analysis of the T-cell repertoire of the blood samples collected from the patients at baseline, during the treatment period with Posoleucel VSTs, and during the following period (post-treatment). Sequencing results were analyzed using the ImmunoSEQ® Analyzer to identify unique line-derived clonotypes that were shared between the infused line (Posoleucel treatment) and the recipient PBMCs postinfusion but are absent from baseline PBMCs (pre-infusion).

The persistence of virus-specific T cells (VSTs), as reflected by the number of unique TCRs, was measured at baseline (week 0, pre-VST treatment with Posoleucel), week 4 during the treatment period, week 12 during the treatment period and week 24 of the study (week 12 of the follow-up period). These unique TCRs refer to TCRs that were present in Posoleucel treated patients but not present in patient samples at Baseline.

Posoleucel VSTs were observed in the patient samples taken at weeks 4, 12, and 24 (FIG. 6A). These interim results (samples from four patients were evaluated at weeks 0, 4, and 12 and samples from three patients were evaluated at weeks 0, 4, 12, and 24) provide evidence that VSTs generated from Posoleucel treatment persisted at least until week 24 of the study (z.e., at least 12 weeks following the last infusion at week 12). At the completion of the study, samples from 35 patients that received Posoleucel were analyzed to assess persistence of Posoleucel. When stratifying by treatment group, persistence of Posoleucel VSTs was observed in all cohorts throughout the study period (FIG. 6B), though a higher sum frequency of PSL- derived clones was detected in the stable IS/high viral load group versus the stable IS/low viral load group (FIG. 12).

In addition, Enzyme-Linked Immunospot (ELIspot) analysis was used to quantitate the frequency of IFNy-secreting cells at baseline (pre-treatment) as well as at weeks 2, 4, 6, 8, 12, 16, 20, 24 post PSL treatment when sufficient samples were available. PBMCs were isolated from whole blood and antigen-specific activity was measured after direct stimulation of PBMCs with LT and VP1 BK antigen pepmixes. After 20 hours of incubation, spotforming cells (SFC) were determined per 5xl0e5 PBMCs. Functional T cells (BK-reactive IFN-y+) were confirmed in six of the seven patient samples analyzed by ELISpot assay.

Posoleucel is a multi-virus specific T cell product with specificity for BKV, AdV, CMV, EBV, and HHV-6 (with additional cross-reactive specificity for JCV). Without being bound by theory, these data suggest that the persistence of Posoleucel in BK viremia patients treated with Posoleucel may also provide protection against the five other viruses targeted by Posoleucel.

Example 4. Change in BK Viral Load in Patients during and after treatment with Posoleucel

BK viral load was assessed in patients following treatment with Posoleucel and compared between patients treated in Arm 1 (Regimen A) also known as the “active” protocol and patients treated in Arm 2 (Regimen B) also known as the “hybrid” protocol. In general, patients treated with the active protocol experienced a greater change in viral load between baseline and 24 weeks as compared to patients who received the hybrid protocol.

Patients were treated with Posoleucel as described in Example 2. Plasma samples were taken from patients to assay for BK viral load at the following time points:

A. Period 1 (the treatment period) at: 1-2 weeks before the start of the study, study day 1, study day 15 (± 3 days), study day 29 (± 3 days), study day 43 (± 3 days), study day 71 (± 3 days), and study day 85 (± 3 days); and

B. Period 2 (the follow-up period) at: study day 99 (± 7 days), study day 113 (± 7 days), study day 127 (± 7 days), study day 141 (± 7 days), study day 155 (± 7 days), and study day 169 (± 7 days).

The viral load in the plasma samples from the patients was assessed at a central lab using the BKV EliTech MGB Alert ASR quantitative polymerase chain reaction (qPCR) Hss&y .

An interim analysis of the data was conducted to compare BK viral load between the active (n ^:: 41) and hybrid (n 45) groups. A decrease in BK viral load was observed in patients in both the active and hybrid groups (FIGs. 7A and 7B). In general, more patients in the Q14d (active) treatment group experienced a greater decrease in viral load than those in the Q28d (hybrid) group. The BK viral load of at least three patients in the active treatment group fell below the lower limit of quantitation (LLOQ) and the BK viral load of at least two patients in the hybrid treatment group fell below the LLOQ.

In addition the Logio change in viral load from baseline (pre-VST treatment Day 1) was analyzed as an interim analysis (FIGs. 7C and 7D). Several patients in both the active and hybrid groups experienced a decrease in viral load from baseline. In general, patients in the active group experienced a greater decrease in viral load from baseline than those in the hybrid group.

The clinical goal for reducing viral load (a clinically meaningful BKV viral load reduction) was achieving at least a 1 logjo reduction in viral load. Here, a progressive reduction in viral load was also observed. These data suggest that the viral load was reduced overtime following Posoleucel infusion (Figs. 7A-7D).

FIGs. 8A and 8B depict the mean and median Logio change in BK viral load from baseline for the Q14d (active) and Q28d (hybrid) patient groups at interim analysis. The Q14d group experienced a greater mean and median decrease in viral load from baseline than the Q28d group.

An extended data set was analyzed among the three treatment groups to assess BK viral load reduction at the end of the 24-week study period that includes the 12-week treatment period and the 12-week follow-up period. The outcomes of patients with stable immunosuppression (IS) in the 30 days (+/- 2) before randomization into treatment groups were analyzed (Arm 1 (active, n=20), Arm 2 (hybrid, n =18), and placebo (n=14)) for BK viral load reduction (Table 1). Stable immunosuppression was categorized as a <50% reduction of the patient’s major immunosuppressive regimen (z.e., CNI (calcineurin inhibitor), mTOR, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine) within 30 (+/-2) days of randomization. Only patients who completed the study (z.e., were not lost to follow-up or did not withdraw from the study) were analyzed.

As noted above, the key secondary endpoint of the study was the change in BK viral load in patients receiving Posoleucel versus those receiving placebo. The efficacy analysis excluded six patients whose major immunosuppressive regimens (i.e. CNI (calcineurin inhibitor), mTOR, MMF/MPA (mycophenolate mofetil/mycophenolic acid), or azathioprine) were reduced by more than 50% within 30 (+/-2) days of randomization. Posoleucel achieved greater viral load reductions versus placebo across all BK viral load (VL) measures. In week 24 efficacy analysis, 39% (15/38) of patients who received Posoleucel experienced a >l-log viral load reduction, which was more than double the placebo rate (14%; 2/14) (Table 2). Over time and in serial samples (pre, week 14 and week 24) tested, it was observed that more patients in the stable IS/initial high viral load (>10,000 copies/mL) group experienced a progressive decline in viral load in the PSL group versus placebo (FIG. 9) and (Table 2). In particular, in the PSL treated group a greater proportion of patents experienced a reduction in BK viral load of at least 1 log at week 24 of the study (with a tendency to progressive reduction of BK viral load from day 1 to week 14 to week 24) as compared to the placebo treated group. In the same patient cohorts there was a progressive increase in the frequency of BKV-specific ZFNy producing T cells (as measured by ELIspot assay), in stable IS/high viral load patients administered Posoleucel in comparison with the Placebo group (FIG. 10). Posoleucel dose response was observed, with a >l-log viral load reduction in the biweekly dosing group of 50% (10/20) versus 28% (5/18) in the monthly dosing group and 14% (2/14) in the placebo group (Table 1). The greatest effect on BK viral load was seen at week 24 in patients with a high BK viral load (>10,000 copies/mL) at screening who received more frequent dosing (Arm 1): 75% (6/8) achieved a viral load reduction of >1 logio copies/mL from baseline (median change -1.4 log) versus 25% (1/4) of patients in the placebo group (median change -0.4 log). Further, 69% (11/16) of patients who received Posoleucel overall achieved a >l-log viral load reduction (Table 2). Overall, the probability of achieving a viral load reduction of >1 Logio copies/mL increased over the course of the study for Posoleucel treated patients compared to placebo treated patients (FIGs. 11A-11C).

Expansion of BK-specific T cells and persistence of Posoleucel were detected in treated patients throughout the study. Post-infusion, an increase in BK-specific T cells was detected and the presence and persistence of Posoleucel was confirmed by TCRv0 deep sequencing. Patients with stable immunosuppression (IS) were stratified by having an initial low (350 to <10,000 copies/mL) or high (>10,000 copies/mL) viral load, and the sum frequency of Posoleucel-derived clones at week 4, 12, and 24 of the study are presented (FIG. 12). Persistence of Posolecucel clones was detected in both patient populations (high viral load and low viral load). However, at each time point, the high viral load population was associated with increased frequency of Posoleucel-derived clones. These data demonstrate persistence of Posoleucel clones in vivo and a higher frequency of clones in those patients with higher viral loads (FIG. 12) in addition to a higher circulating frequency of functional (fFNy-producing T cells) in the same patient population (FIG. 15B). Without being bound by theory, these data suggest that in vivo viral stimulation may be driving in vivo expansion of PSL cells. No difference in Posoleucel longevity (persistence) was observed between the Q14d and Q28d treatment groups (FIG. 6B).

To determine if there were phenotypic or functional differences between the cells administered to patients with high viral load and low viral load, cell phenotype and reactivity was measured. No difference was observed between the percentage of CD3+, CD4+, and CD8+ cells between patient groups (FIG. 13). IFNy ELISpot assay was used to determine the number of spot forming cells in Posoleucel prior to administration to patients. Stratifying the patients by low and high viral load demonstrates that the Posolecucel cells administered to each patient group have similar potency pre-infusion when exposed to BK viral antigen (FIG. 14). These data demonstrate that the cells administered to each patient group have a similar phenotype and similar potency.

At baseline, select patients appeared to have pre-existing immunity to BK virus (as measured by IFNy ELIspot; FIG. 15A) and these patients typically have low viral load. Notably, 26% of all patients had functional BK T cells prior to study entry, and 75% of those patients were in the low viral load strata. As shown in Fig. 15A, BKV reactive T cells were higher in the low viral load patients prior to administration of Posoleucel. Following infusion of PSL or placebo to patients fold change in IFNy secreting T cells was compared in all patients with stable IS and in those with initial high or low viral loads. The stable IS/high viral load patients had greater increases in BKV-specific IFNy producing T cells versus placebo, while no such difference was seen in the low viral load strata (FIG. 15B). The stable IS/high viral load patients showed a progressive increase in fold change of BKV-specific IFN producing T cells throughout the course of the study (FIG. 15C). These results were similar when broken out into patients dosed on Arm 1 (Q14d) or Arm 2 (Q28d) (FIG. 16).

Without being bound by theory, it is believed that patients with pre-existing immunity to BK virus had a low viral load because their endogenous T cells were actively controlling viral replication. In contrast, patients in the high-viral load group with lower pre-existing immunity saw a greater increase in functional T cells after administration of Posoleucel to fight the infection.

Antiviral responses among Posoleucel patients increased overtime, with maximal responses observed at Week 24. Renal function remained stable throughout the study. No patients had > Grade 3 adverse events (AE), serious adverse events, or episodes of acute rejection assessed as drug related during the study. The safety profile of kidney transplant recipients was similar to that observed in hematopoietic cell transplant patients. Table 1: BK Viral Load Reductions at Week 24 in Patients with Stable Immunosuppression

Before Randomization f2 patients discontinued the study, and 2 had pre-randomization IS reduction.

JI patient discontinued the study, and 4 had pre-randomization IS reduction.

Table 2: Summary of Week 24 Virol ogic Changes Among Patients With Stable Immunosuppression Prior to Randomization

* Excludes one patient who discontinued the study

■ Excludes two patients who discontinued the study

PSL = Posoleucel

PBO = Placebo

VL = Viral Load

These data provide the first demonstration of therapeutic potential of Posoleucel for solid organ transplant patients. Indeed, these data provide support that treatment with Posoleucel VSTs reduces BK viral load in patients that have undergone a solid organ transplant, and they provide evidence that both the active and hybrid treatment protocols reduce viral load (Table 1), with the active protocol providing a greater reduction in viral load. These data also demonstrate a meaningful reduction in BK viral load in patients that had a high viral load at baseline, who are at greatest risk for renal impairment. Further, these data provide support that repeat administration of Posoleucel is generally safe and well tolerated, with repeat dosing over a 12-week period.

FIGs. 17A-17C provides exemplary overviews of three patients treated with Posoleucel and changes in viral load, frequency of I Ny secreting T cells and detection of PSL-derived clones by TCR deep sequencing over the course of the study. The patients were administered Posoleucel 5 months, 1.3 years, and 3 months after receipt of the kidney transplant, respectively (FIGs. 17A-17C).

In sum, Posoleucel demonstrated clinically meaningful antiviral efficacy as compared to placebo, with the response being greater in the biweekly dosing group across all patients. The high viral load stratum (> 10,000 copies/mL) experienced the most profound viral load reductions and highest rates of >1 Logio BK VL decline. Example 5. Reduction in BK Viral Load in Patients with BK Viral Load of > 5,000 copies/mL during and after treatment with Posoleucel

A viral load of >5,000 copies/mL is considered significant in the clinic. Therefore, it was evaluated whether Posoleucel treatment was effective in subjects with a viral load of >5,000 copies/mL. In subjects administered Posoleucel that had stable immunosuppression and a viral load of >5,000 copies/mL, antiviral effects persisted through the end of the study (Table 3). All patients in this group received Posoleucel within two years of receiving a solid organ transplant (Table 3).

Table 3: BK Viral Load Reductions at Week 24 in Patients with Stable Immunosuppression and a BK viral load of >5,000 copies/mL and less than 2 years after transplant**

Overall, the probability of achieving a viral load reduction of >1 Logio copies/mL increased over the course of the study for Posoleucel treated patients compared to placebo treated patients (FIGs. 18A-18C). The p value is based off the Log-Rank Test. Example 6: Increased HLA Matching with Transplant Tissue Improves Anti-Viral Response

Patients were evaluated to determine if HLA matching altered the rate of response to treatment with Posoleucel. The overall level of HLA matching between the transplanted organ and infused patients is shown (FIG. 19). Patients in receipt of VST lines matched at greater than three shared alleles (high allele match) versus two or three shared alleles (low allele match) between the Posoleucel cell line (VST) and the transplant tissue demonstrated a superior anti-viral response. (Table 4). High (> 2) versus low (1 - 2) allele matching between the patient and the Posoleucel cell line did not impact response rate (Table 5). Together, these data demonstrate the importance of allele matching between the transplant tissue and the Posoleucel cell line for improving response rate to treatment. Posoleucel infusions were determined to be safe irrespective of whether patients had low or high viral load.

Table 4: Allele Matching of Transplant to VSTs and Rate of Response Table 5: Allele Matching of Patient to VSTs and Rate of Response

Example 7: Treatment with Posoleucel and Estimated Glomerular Filtration Rate

Throughout the study, the estimated glomerular filtration rate (eGFR) was monitored in patients. A reduced eGFR is reflective of reduced kidney function. Median eGFR remained stable throughout the study in all groups, with a median change in estimated glomerular filtration rate from baseline to Week 24 of 0 mL/min/1.73m ² in the overall Posoleucel group and 0 mL/min/1.73m ² in the placebo group (Table 6). Similar change is observed in eGFR when stratifying by viral load (Table 7).

Following completion of Posoleucel administration a subset of patients were monitored for changes in eGFR at week 36, week 48, week 60, and one patient to week 72. Preliminary data suggests patients administered Posoleucel maintain a stable eGFR while patients treated with placebo have a reduction in eGFR from baseline (FIG. 20A). Preliminary results show a similar pattern when stratified by treatment arm (FIG. 20B). In particular, both treatment arms (Q28 and Q14) demonstrate slower reduction in eGFR levels as compared to placebo with the Q28 arm demonstrating an overall improvement in eGFR levels (FIG. 20B). Together, these data suggest that treatment with Posoleucel helps maintain kidney function over time. Table 6: eGFR at Week 12 and 24 in Patients with Stable Immunosuppression

* Stable IS: No or <50% Reduction of CNI or mTOR or MPA or Aza during 30 (+2) days before randomization

Table 7: eGFR at Week 12 and 24 in Patients with Stable Immunosuppression by Viral Load

Example 8. Posoleucel Reduces BK Viral Load Following Allogeneic Hematopoietic Stem Cell Transplant

Posoleucel was evaluated in a Phase 2 clinical trial where repetitive (up to 7) infusions of VSTs were administered to allogeneic hematopoietic stem cell transplant (HSCT) patients prophylactically/pre-emptively to prevent clinically significant infections and/or end organ disease associated with the Posoleucel target viruses BKV, CMV, AdV, EBV, HHV-6 and/or JCV.

Viral loads associated with each of the target viruses was measured prior to administration of the VSTs and serially over the course of the primary endpoint (14 weeks following the first administration). FIG. 21 shows data related to BK virus, demonstrating an inverse relationship between detectable, BK-specific T cells and viral load in those with available samples who reactivated BK virus (FIG. 21).