ANTI-MYCT1 ANTIBODIES AND USES THEREOF

CROSS REFERENCE

[0001 ] The present application claims the benefit of U.S. Provisional Patent Application No. 63/357,888, entitled, “ANTI-MYCT1 ANTIBODIES AND USES THEREOF” filed July 1 , 2023, the content of which is hereby incorporated by reference in its entirety.

FIELD OF THE TECHNOLOGY

[0002] The present disclosure relates, in general, to compositions comprising anti-MYCT1 antibodies and methods for modulating MYCT1 activity. More specifically, the present disclosure provides compositions and methods which prevent or reduce tumor angiogenesis, remodels tumor immunity, and improves immunotherapy outcomes.

INCORPORATION OF SEQUENCE LISTING

[0003] This present application contains a Sequence Listing which has been submitted in .XML format via Patent Center and is hereby incorporated by reference in its entirety. Said WIPO Sequence Listing was created on July 3, 2023, XML copy is named 760394. xml, and is 137 kilobytes in size.

BACKGROUND

[0004] Angiogenesis and immune tolerance are both normal physiologic mechanisms that are hijacked by tumors. Angiogenesis involves the formation of new vessels from preexisting ones during development and wound healing. The modulation of angiogenesis is highly regulated by proangiogenic and antiangiogenic factors, a process that becomes disrupted and dysregulated in cancer. Tumor-driven hypoxia increases the expression of proangiogenic factors leading to the formation of new vessels that are vital to the tumor survival and proliferation. The VEGF family, consisting of six growth factors (VEGFA-F), plays the most critical role in angiogenesis by binding to their receptors VEGFR1 -3 and neuropilin. Angiogenesis can also be mediated by the angiopoietin (Ang1-2)/Tie-2 pathway, independent from the VEGF pathway. Accordingly, drug development was heavily focused on anti-angiogenesis in the past decade as a strategy to deprive tumor's nutrition and inhibit tumor growth. However, despite the modest activities of these agents as single agents or in combination with chemotherapy, tumors can overcome their effects and become resistant.

[0005] Cancer immunotherapy has emerged as a modality that can effectively treat a variety of cancers with the discovery of immune checkpoints. A plethora of investigations with immune checkpoint inhibitors (ICI) has demonstrated a long-lasting clinical activity against many malignancies. ICIs block another mechanism hijacked by tumor “immune exhaustion,” unleashing the effector immune cells against cancer. Primary resistance to ICIs is described in tumors that lack tumor-infiltrating lymphocytes. In addition, tumors that initially respond to ICIs can develop secondary resistance due to defects in antigen-presenting machinery and the overexpression of coinhibitory molecules among other factors.

[0006] Accordingly, there is a need in the art for compositions and methods which address angiogenesis and immune exhaustion in tumor cells. SUMMARY

[0007] In some aspects, provided herein is an isolated anti-MYCT1 antibody or a fragment thereof, that specifically binds an epitope within the first 100 amino acids of SEQ ID NO:145. In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof of comprises a light chain variable region comprising an L1 with amino acid sequence of SEQ ID NO: 28, SEQ ID NO: 64, SEQ ID NO: 100, or SEQ ID NO: 136, an L2 with amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 66, SEQ ID NO: 102, or SEQ ID NO: 138, an L3 with amino acid sequence of SEQ ID NO: 32, SEQ ID NO: 68, SEQ ID NO: 104, or SEQ ID NO: 140 or any combination thereof; and/or a heavy chain variable region comprising an H1 with amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 46, SEQ ID NO: 82, or SEQ ID NO: 118, an H2 with amino acid sequence of SEQ ID NO: 12, SEQ ID NO: 48, SEQ ID NO: 84, or SEQ ID NO: 120, an H3 with amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 50, SEQ ID NO: 86, or SEQ ID NO: 122, or any combination thereof. [0008] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof of, comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 36, SEQ ID NO: 72, SEQ ID NO: 108, or SEQ ID NO: 144; and/or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 18, SEQ ID NO: 54, SEQ ID NO: 90, or SEQ ID NO: 126, or any combination thereof.

[0009] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises a light chain variable region comprising an L1 with amino acid sequence of SEQ ID NO: 28, an L2 with amino acid sequence of SEQ ID NO: 30, an L3 with amino acid sequence of SEQ ID NO: 32, or any combination thereof; and/or a heavy chain variable region comprising an H1 with amino acid sequence of SEQ ID NO: 10, an H2 with amino acid sequence of SEQ ID NO: 12, an H3 with amino acid sequence of SEQ ID NO: 14, or any combination thereof.

[0010] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises a light chain variable region comprising an L1 with amino acid sequence of SEQ ID NO: 64, an L2 with amino acid sequence of SEQ ID NO: 66, an L3 with amino acid sequence of SEQ ID NO: 68, or any combination thereof; and/or a heavy chain variable region comprising an H1 with amino acid sequence of SEQ ID NO: 46, an H2 with amino acid sequence of SEQ ID NO: 48, an H3 with amino acid sequence of SEQ ID NO: 50, or any combination thereof.

[0011 ] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises a light chain variable region comprising an L1 with amino acid sequence of SEQ ID NO: 100, an L2 with amino acid sequence of SEQ ID NO: 102, an L3 with amino acid sequence of SEQ ID NO: 104, or any combination thereof; and/or a heavy chain variable region comprising an H1 with amino acid sequence of SEQ ID NO: 82, an H2 with amino acid sequence of SEQ ID NO: 84, an H3 with amino acid sequence of SEQ ID NO: 86, or any combination thereof.

[0012] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises a light chain variable region comprising an L1 with amino acid sequence of SEQ ID NO: 136, an L2 with amino acid sequence of SEQ ID NO: 138, an L3 with amino acid sequence of SEQ ID NO: 140, or any combination thereof; and/or a heavy chain variable region comprising an H1 with amino acid sequence of SEQ ID NO: 118, an H2 with amino acid sequence of SEQ ID NO: 120, an H3 with amino acid sequence of SEQ ID NO: 122, or any combination thereof.

[0013] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises an amino acid sequence of the light chain variable region of SEQ ID NO: 36 and/or an amino acid sequence of the heavy chain variable region of SEQ ID NO: 18.

[0014] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises an amino acid sequence of the light chain variable region of SEQ ID NO: 72 and/or an amino acid sequence of the heavy chain variable region of SEQ ID NO: 54.

[0015] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises an amino acid sequence of the light chain variable region of SEQ ID NO: 108 and/or an amino acid sequence of the heavy chain variable region of SEQ ID NO: 90.

[0016] In some aspects, the isolated anti-MYCT1 antibody or a fragment thereof, comprises an amino acid sequence of the light chain variable region of SEQ ID NO: 144 and/or an amino acid sequence of the heavy chain variable region of SEQ ID NO: 126.

[0017] In some aspects, the isolated antibody or a fragment thereof of any disclosed herein is a monoclonal antibody. In some aspects, the isolated antibody or a fragment thereof is a humanized antibody, a single chain variable fragment (scFv) antibody, an antibody fragment, or a chimeric antibody.

[0018] In some aspects, further provided is a pharmaceutical composition comprising a disclosed isolated antibody or a fragment thereof and a pharmaceutically acceptable carrier or excipient. In some aspects, the isolated antibody is for use as a medicament.

[0019] The disclosure further encompasses a method of treating a cancer in a subject in need thereof, the method comprising administering an effective amount of a composition comprising an isolated antibody or a fragment thereof, disclosed herein. In some aspects, the method further comprises administering an immune checkpoint inhibitor and, optionally, anti-VEGF targeted therapy.

[0020] In further aspects, the disclosure encompasses a method of sensitizing a cancer to an immune checkpoint inhibitor in a subject, the method comprising, selecting a subject with a cancer, wherein the cancer is resistant to an immune checkpoint inhibitor; and administering to the subject an effective amount of a composition comprising a disclosed isolated antibody or a fragment thereof. In some aspects of the method, the administration of the anti-MYCT1 antibody results in reduction in angiogenesis in cancer cells of the subject. In some aspects of the method, the administration of the anti-MYCT1 antibody results increase in anti-tumor immunity in the subject. In some aspects of the method, the administration of the anti-MYCT1 antibody results in reduction of tumor volume in the subject.

[0021 ] Further provided is a method of regulating tumor angiogenesis and/or increasing anti-tumor immunity in a subject having a cancer, the method comprising: administering to the subject a therapeutically effective amount of composition comprising an isolated antibody or a fragment thereof disclosed herein. In some aspects, the method further comprises administering an immune checkpoint inhibitor and, optionally, VEGF inhibitor.

BRIEF DESCRIPTION OF THE FIGURES

[0022] Those of skill in the art will understand that the drawings, described below, are for illustrative purposes only. The drawings are not intended to limit the scope of the present teachings in any way.

[0023] FIG. 1A-1D show generation of anti-MYCT1 antibodies. FIG. 1A shows the sequence alignment of human MYCT1 isoform 1 (SEQ ID NO: 1 5) and mouse MYCT1 amino acid sequences (SEQ ID NO: 150). FIG. 1B shows the immunization scheme to generate MYCT1 monoclonal antibodies. LS, lumazine synthase (LS) from the hyperthermophile Aquifex aeolicus (AaLS), keyhole limpet haemocyanin (KLH), bovine serum albumin (BSA), HUVEC, human umbilical vein endothelial cell (HUVEC), mouse cardiac endothelial cell (MCEC), enzyme-linked immunosorbent assay (ELISA), fluorescence-activated cell sorting (FACS), KD, knockdown (KD), over-expression (OE). FIG. 1C shows a graph of a representative MYCT1 terminal sera titration from fusion no. 4941 (animal No. 8). MYCT1 antigen was added at 1 pg/ml. FIG. 1D shows a graph of a representative MYCT1 terminal sera titration from fusion no. 4952 (animal No. 2). MYCT1 antigen was added at 1 pg/ml.

[0024] FIG. 2A-2E show the plasmid map of plasmids used in studies disclosed herein.

[0025] FIG. 3A-3D show initial screening results of generated monoclonal antibodies. FIG. 3A shows results from ELISA assay. FIG. 3B shows results from fluorescence-activated cell sorting (FACS), mouse cardiac endothelial cell (MCEC), over-expression (OE). FIG. 3C and FIG. 3D show representative result and images from scratch assay at 3 hours.

[0026] FIG. 4A-4C show screening results using the plasmid pcDNA3.1- Myctl Flag shown in FIG. 2A. FIG. 4A shows results from FACS. FIG. 4B and FIG 4C show representative images results from scratch assay.

[0027] FIG. 5A-5B show identification of anti-MYCT1 antibody clones. FIG. 5A shows identification of clones 2B4 (lgG2b isotype) and 11 B6(lgG1 isotype) based on scratch assay, FACS staining, and ELISA. FIG. 5B shows identification of clones 3E3, 8D12, 9E2, and 9F8 based on scratch assay, FACS staining, and ELISA.

[0028] FIG. 6A-6C show characterization of antibody clone 2B4F9D9. FIG. 6A shows FACS using hybridoma supernatant containing candidate antibody 2B4F9D9 in overexpressing HA-Mouse Myctl over-expression (HA-mMOE) murine cardiac endothelial cell (MCEC). FIG. 6B and FIG. 6C show representative images and results from scratch assay using antibody clone 2B4F9D9.

[0029] FIG. 7A-7C show results from sprouting assay for 15 hours in inducible Murine Lung Endothelial Cell (iMLEC) treated with purified antibody clones. FIG. 7A shows representative images of sprouting assay in iMLEC cells and iMLEC Mytcl KO cells. FIG. 7B shows sprouts per beads in iMLEC cells and iMLEC Mytcl KO cells. FIG. 7C show sprouting length in iMLEC cells and iMLEC Mytcl KO cells. **p<0.01, ***p<0.001, **** p <0.0001 compared IgG treated cells, one-way ANOVA. [0030] FIG. 8A-8C show results from sprouting assay for 30 hours in MCEC treated with purified antibody clones. FIG. 8A shows representative images of sprouting assay in MCEC cells. FIG. 8B shows sprouts per beads in MCEC cells. FIG. 8C show sprouting length in MCEC cells. **p<0.01 compared IgG treated cells, one-way AN OVA.

[0031 ] FIG. 9A-9G show results from sprouting assay in MCEC cells or inducible human umbilical vein endothelial cell (iHUVEC) cells treated with purified antibody clones 3EC12, 8D2C12, 9E2H5 and 2B4F9D3. FIG. 9A shows representative images of sprouting assay in MCEC cells. FIG. 9B shows sprouts per beads in MCEC cells, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 versus HM treated Group, one-way ANOVA. FIG. 9C show sprouting length in MCEC cells. ***p<0.001, ****p<0.0001 versus HM treated Group, one-way ANOVA. FIG. 9D show representative images of sprouting assay in iHUVEC cells treated at increasing concentrations of antibody clone 11 B6 or 2B4F9D3 for 24 hours. FIG. 9E show representative images of sprouting assay in iHUVEC cells treated at increasing concentrations of antibody clone 11 B6 or 2B4F9D3 for 48 hours. FIG. 9F show graphs of sprouts number and sprouts length in iHUVEC cells treated at increasing concentrations of antibody clone 11 B6 or 2B4F9D3 for 24 hours. * p<0.05 versus IgG treated cells, 2-way ANOVA. FIG. 9G show graphs of sprouts number and sprouts length in iHUVEC cells treated at increasing concentrations of antibody clone 11 B6 or 2B4F9D3 for 48 hours. * p<0.05, ***p<0.001, ****p<0.0001 versus IgG treated cells, 2-way ANOVA.

[0032] FIG. 10A-10E show results from tube formation assay with purified antibody clones. FIG. 10A shows representative images of tube formation in iMLEC cells treated with 4pg/well of 11 B6 and 2B4F9D3 for 4 hours. FIG. 10B shows representative images of tube formation in MCEC cells treated with 2B4F9D3, 3EC12, 8D2C12 and 9E2H5. FIG. 10C show number of loop in each treatment in MCEC. **p<0.01, ***p<0.001 versus HM treated cells, one-way ANOVA. FIG. 10D show tube formation in iHUVEC cells treated at increasing concentrations of 11 B6 or 2B4F9D3 for 16 hours. Scale Bar=100pm. FIG. 10E show loop and branch number in treated iHUVEC cells. * p<0.05, **p<0.01 versus IgG treated cells, 2-way ANOVA. [0033] FIG. 11 A-11 F show results from scratch assay from cells treated with hybridoma supernatants. FIG. 11A shows representative images of wound closure in MCEC cells treated with hybridoma supernatants of antibody clones 11 B6, 2B4F9D3 or IgG added at 32pg/well at 0 hours, 8 hours and 10 hours. FIG. 11B shows a graph depicting relative closure tube in MCEC cells treated with hybridoma supernatants of 11 B6, 2B4F9D3, or IgG. * p<0.05, **p<0.01 versus IgG treated cells, 2-way ANOVA. FIG. 11C shows representative images of wound closure in iMLEC cells treated with hybridoma supernatants of 11 B6, 2B4F9D3, or IgG added at 32pg/well and iMLEC Myctl knock-out (MKO) cells at 0 hours, 9 hours and 11 hours. FIG. 11 D shows a graph depicting relative closure tube in iMLEC cells treated with hybridoma supernatants of 11 B6, 2B4F9D3, or IgG and iMLEC MKO cells. * p<0.05, **p<0.01 versus IgG treated cells, 2-way ANOVA. FIG. 11 E shows representative images of wound closure in MCEC cells treated with hybridoma supernatants of 3E3C12, 8D2C12, 9E2H5, 2B4F9D3, or IgG added at 50pg/well at 0 hours, and 9 hours. FIG. 11 F shows a graph depicting relative closure tube in MCEC cells treated with hybridoma supernatants of 3E3C12, 8D2C12, 9E2H5, 2B4F9D3 or HM. **p<0.01, ****p<0.0001 versus HM treated cells, one-way ANOVA.

[0034] FIG. 12A-12F shows in vivo characterization of 2B4F9D3 and 11 B6 using a tumor model. FIG. 12A and FIG. 12C show a scheme of 11 B6 or 2B4F9D3 injection with a-PD1 antibody treatment using 1956 sarcoma line. FIG. 12B and FIG. 12D show tumor growth in PBS injected (control), a-PD1 alone, 2B4F9D3 + a-PD1 , or 11 B6 + a-PD1 treated mice. FIG. 12E shows a scheme of 11 B6 or 2B4F9D3 injection with a-PD1 antibody treatment using PyMT-BO1 orthotopic breast tumor model. FIG. 12F show tumor growth in PBS injected (control), a-PD1 alone, 2B4F9D3 + a-PD1 , or 11 B6 + a-PD1 treated mice. FIG. 12G show combined line graph of tumor growth, a- PD1 , 250pg/injection/mouse, 2B4 and 11 B6, 330pg/injection/mouse. All antibodies were injected i.p.

DETAILED DESCRIPTION

[0035] Both immune checkpoint inhibitors (ICI) and anti-angiogenesis agents have changed the landscape of cancer treatment in the modern era. While anti- angiogenesis agents have demonstrated activities in tumors with high vascularization, including renal cell carcinoma and colorectal cancer, the effect of ICIs has been seen mainly in immunologically recognized tumors, with highly immune-infiltrative lymphocytes. The main challenge in the drug development of ICIs is moving their activities to noninflamed tumors and overcoming resistance that is driven, in part, by the immune-suppressive microenvironment. Angiogenesis factors drive immune suppression by directly suppressing the antigen-presenting cells as well as immune effector cells or through augmenting the effect of regulatory T cells (Treg), myeloid- derived suppressor cells (MDSC), and tumor-associated macrophages (TAM). Those suppressive immune cells can also drive angiogenesis, creating a vicious cycle of impaired immune activation. Applicants have discovered that compositions and certain methods comprising MYCT1 reduce or prevent tumor growth, reduce or prevent tumor angiogenesis (i.e. , the formation and development of the vasculature that tumors need in order to thrive and progress), and/or increase tumor immune response.

[0036] MYCT1 proteins, appears dispensable for homeostatic angiogenesis signaling, but necessary for the maintenance of immune-suppressive tumor vasculature and tumor microenvironment (Kabir et al., Sci. Transl. Med. 13, eabb6731 (2021 ) content of which is herein incorporated by reference). The present disclosure is based, in part, on the identification of anti-MYCT1 monoclonal antibodies which specifically binds an epitope within extracellular region of MYCT1 protein. MYCT1 protein exists in two isoforms in humans. One isoform has a sequence with 235 amino acids (referred herein as isoform 1 ), and a second isoform which is shorter, with 187 amino acids (referred herein as isoform 2). The amino acids 1-19 of mouse MYCT1 is identical to amino acids 48-67 of human MYCT1 isoform 1 (FIG. 1A) and amino acids 1 - 19 of human MYCT1 isoform 2. This conserved region of MYCT1 was targeted for generation of antibodies herein. The disclosed antibodies generated using this extracellular region of MYCT1 have wide applicability, including neutralizing activity against both human MYCT1 protein and mouse MYCT1 protein. Thus, the present disclosure encompasses use of compositions and methods comprising anti-MYCT1 antibodies to treat a tumor or cancer in a subject. In particular, the present disclosure provides that MYCT1 expression and/or activity is required in controlling tumor angiogenesis and reprogramming tumor immunity. Further provided herein are compositions and methods which down-regulate MYCT1 activity and/or expression in cells (e.g., endothelial cells). The down-regulation of MYCT1 is associated with reduced angiogenesis, enhanced endothelial venule formation, and promoted an anti-tumor immune environment, leading to restricted tumor progression. Accordingly, the present disclosure provides compositions and methods for reducing or preventing angiogenesis and increasing tumor immune response.

[0037] Other aspects and iterations of the invention are described more thoroughly below.

I. Terminology

[0038] So that the present invention may be more readily understood, certain terms are defined. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which aspects of the invention pertain. Many methods and materials similar, modified, or equivalent to those described herein can be used in the practice of the aspects of the present invention without undue experimentation, the preferred materials and methods are described herein. In describing and claiming the aspects of the present invention, the following terminology will be used in accordance with the definitions set out below.

[0039] The term "a" or "an" entity refers to one or more of that entity; for example, a "polypeptide subunit" is understood to represent one or more polypeptide subunits. As such, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein.

[0040] The term “about,” as used herein, refers to variation of in the numerical quantity that can occur, for example, through typical measuring techniques and equipment, with respect to any quantifiable variable, including, but not limited to, mass, volume, time, distance, and amount. Further, given solid and liquid handling procedures used in the real world, there is certain inadvertent error and variation that is likely through differences in the manufacture, source, or purity of the ingredients used to make the compositions or carry out the methods and the like. The term “about” also encompasses these variations, which can be up to ± 5%, but can also be ± 4%, 3%, 2%, 1 %, etc. Whether or not modified by the term “about,” the claims include equivalents to the quantities.

[0041 ] The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e. , elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and/or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and/or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one aspect, to A only (optionally including elements other than B); in another aspect, to B only (optionally including elements other than A); in yet another aspect, to both A and B (optionally including other elements); etc.

[0042] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0043] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and/or B”) can refer, in one aspect, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another aspect, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another aspect, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0044] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Any reference to “or” herein is intended to encompass “and/or” unless otherwise stated. Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “at least,” “greater than” or “greater than or equal to” applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1 , 2, or 3 is equivalent to greater than or equal to 1 , greater than or equal to 2, or greater than or equal to 3.

[0045] Whenever the term “no more than,” “less than,” “less than or equal to,” or “at most” precedes the first numerical value in a series of two or more numerical values, the term “no more than,” “less than” or “less than or equal to,” or “at most” applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1 .

[0046] Where values are described as ranges, it will be understood that such disclosure includes the disclosure of all possible sub-ranges within such ranges, as well as specific numerical values that fall within such ranges irrespective of whether a specific numerical value or specific sub-range is expressly stated.

[0001 ] The components to be used to prepare the disclosed compositions as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules of the compound are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific aspect or combination of aspects of the disclosed methods.

[0002] As used herein, the term “non-naturally occurring” substance, composition, entity, and/or any combination of substances, compositions, or entities, or any grammatical variants thereof, is a conditional term that explicitly excludes, but only excludes, those forms of the substance, composition, entity, and/or any combination of substances, compositions, or entities that are well-understood by persons of ordinary skill in the art as being “naturally-occurring,” or that are, or might be at any time, determined or interpreted by a judge or an administrative or judicial body to be, “ natu ra I ly-occu rring . ”

[0003] By "specifically binds," it is meant that a binding molecule, e.g., an antibody or antigen-binding fragment thereof binds to an epitope via its antigen binding domain, and that the binding entails some recognition between the antigen binding domain and the epitope. According to this definition, a binding molecule is said to "specifically bind" to an epitope when it binds to that epitope, via its antigen-binding domain binds more readily than it would bind to a random, unrelated epitope.

[0004] The portion of a target polypeptide that specifically interacts with the antigen binding domain of an antibody is an “epitope.” Furthermore, it should be noted that an “epitope” on MYCT1 can be a linear epitope or a conformational epitope, and in both instances can include non-polypeptide elements, e.g., an epitope can include a carbohydrate or lipid side chain. The term “affinity” refers to a measure of the strength of the binding of an individual epitope with an antibody’s antigen binding site.

[0005] The term “antibody,” as used herein, is used in the broadest sense and encompasses various antibody and antibody-like structures, including but not limited to full-length monoclonal, polyclonal, and multispecific (e.g., bispecific, trispecific, etc.) antibodies, as well as heavy chain antibodies and antibody fragments provided they exhibit the desired antigen-binding activity. The domain(s) of an antibody that is involved in binding an antigen is referred to as a “variable region” or “variable domain,” and is described in further detail below. A single variable domain may be sufficient to confer antigen-binding specificity. Preferably, but not necessarily, antibodies useful in the discovery are produced recombinantly. Antibodies may or may not be glycosylated, though glycosylated antibodies may be preferred. An “isolated” antibody is one which has been separated from a component of its natural environment. In some aspects, an antibody is purified to greater than 95% or 99% purity as determined by methods known in the art. [0006] In addition to antibodies described herein, it may be possible to design an antibody mimetic or an aptamer using methods known in the art that functions substantially the same as an antibody of the invention. An “antibody mimetic” refers to a polypeptide or a protein that can specifically bind to an antigen but is not structurally related to an antibody. Antibody mimetics have a mass of about 3 kDa to about 20 kDa. Non-limiting examples of antibody mimetics are affibody molecules, affilins, affimers, alphabodies, anticalins, avimers, DARPins, and monobodies. Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Aptamers interact with and bind to their targets through structural recognition, a process similar to that of an antigen-antibody reaction. Aptamers have a lower molecular weight than antibodies, typically about 8-25 kDa.

[0007] The terms “full length antibody” and “intact antibody” may be used interchangeably, and refer to an antibody having a structure substantially similar to a native antibody structure or having heavy chains that contain an Fc region as defined herein. The basic structural unit of a native antibody comprises a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one "light” chain (about 25 kDa) and one "heavy" chain (about 50-70 kDa). Light chains are classified as gamma, mu, alpha, and lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, and define the antibody's isotype as IgG, IgM, IgA, IgD and IgE, respectively. The amino-terminal portion of each light and heavy chain includes a variable region of about 100 to 110 or more amino acid sequences primarily responsible for antigen recognition (VL and VH, respectively). The carboxy-terminal portion of each chain defines a constant region primarily responsible for effector function. Within light and heavy chains, the variable and constant regions are joined by a "J" region of about 12 or more amino acid sequences, with the heavy chain also including a "D" region of about 10 more amino acid sequences. Intact antibodies are properly cross-linked via disulfide bonds, as is known in the art.

[0008] The variable domains of the heavy chain and light chain of an antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three hypervariable regions (HVRs). (See, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007).) A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991 ).

[0009] “Framework region” or “FR” refers to variable domain residues other than hypervariable region (HVR) residues. The FR of a variable domain generally consists of four FR domains: FR1 , FR2, FR3, and FR4. Accordingly, the HVR and FR sequences generally appear in the following sequence: FR1-HVR1-FR2-HVR2-FR3- HVR3-FR4. The FR domains of a heavy chain and a light chain may differ, as is known in the art.

[0010] The term “hypervariable region” or “HVR” as used herein refers to each of the regions of a variable domain which are hypervariable in sequence (also commonly referred to as “complementarity determining regions” or “CDR”) and/or form structurally defined loops (“hypervariable loops”) and/or contain the antigen-contacting residues (“antigen contacts”). Generally, antibodies comprise six HVRs: three in the VH (H1 , H2, H3), and three in the VL (L1 , L2, L3). As used herein, “an HVR derived from a variable region” refers to an HVR that has no more than two amino acid substitutions, as com-pared to the corresponding HVR from the original variable region. Exemplary HVRs herein include: (a) hypervariable loops occurring at amino acid residues 26-32 (L1 ), 50-52 (L2), 91 -96 (L3), 26-32 (H1 ), 53-55 (H2), and 96-101 (H3) (Chothia and Lesk, J. Mol. Biol. 196:901 -917 (1987)); (b) CDRs occurring at amino acid residues 24- 34 (L1 ), 50-56 (L2), 89-97 (L3), 31 -35b (H1 ), 50-65 (H2), and 95-102 (H3) (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991 )); (c) antigen contacts occurring at amino acid residues 27c-36 (L1 ), 46-55 (L2), 89-96 (L3), 30-35b (H1 ), 47-58 (H2), and 93-101 (H3) (MacCallum et al. J. Mol. Biol. 262: 732-745 (1996)); (d) CDR1 -IMGT (positions 27-38), CDR2-IMGT (positions 56-65), and CDR3-IMGT regions (positions 105-116 or 105-117), which are based on IMGT unique numbering (Lefranc, “The IMGT unique numbering for Immunoglobulins, T cell receptors and Ig-like domains,” The Immunologist, 1999, 7: 132-136; Lefranc et al., Nucleic Acids Research, 2009, 37(Database issue): D1006-D1012; Ehrenmann et al., “Chapter 2: Standardized Sequence and Structure Analysis of Antibody Using IMGT,” in Antibody Engineering Volume 2, Eds. Roland E. Kontermann and Stefan Dubel, 2010, Springer-Verlag Berlin Heidelberg, doi: 10.1007/978-3-642-01147-4; imgt.org/IMGTScientificChart/Nomenclature/IMGT-FRCDRdefiniti on), and (e) combinations of (a), (b), (c), and/or (d), as defined below for various antibodies of this disclosure. Unless otherwise indicated, HVR residues and other residues in the variable domain (e.g., FR residues) that are assigned sequence identification numbers are numbered based on IMGT unique numbering, supra.

[0011 ] The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one aspect, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-term inus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991.

[0012] A “variant Fc region” comprises an amino acid sequence that can differ from that of a native Fc region by virtue of one or more amino acid substitution(s) and/or by virtue of a modified glycosylation pattern, as compared to a native Fc region or to the Fc region of a parent polypeptide. In an example, a variant Fc region can have from about one to about ten amino acid substitutions, or from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide. The variant Fc region herein may possess at least about 80% homology, at

Yl least about 90% homology, or at least about 95% homology with a native sequence Fc region and/or with an Fc region of a parent polypeptide.

[0013] An “antibody fragment” refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that binds the antigen to which the intact antibody binds. Non-limiting examples of antibody fragments include but are not limited to Fv, Fab, Fab', Fab'-SH, F(ab')2; single-chain forms of antibodies and higher or-der variants thereof; single-domain antibodies, and multi-specific antibodies formed from antibody fragments.

[0014] Single-chain forms of antibodies, and their higher order forms, may include, but are not limited to, single-domain antibodies, single chain variant fragments (scFvs), divalent scFvs (di-scFvs), trivalent scFvs (tri-scFvs), tetravalent scFvs (tetra- scFvs), diabodies, and triabodies and tetrabodies. ScFv’s are comprised of heavy and light chain variable regions connected by a linker. In most instances, but not all, the linker may be a peptide. A linker peptide is preferably from about 5 to 30 amino acids in length, or from about 10 to 25 amino acids in length. Typically, the linker allows for stabilization of the variable domains without interfering with the proper folding and creation of an active binding site. In preferred aspects, a linker peptide is rich in glycine, as well as serine or threonine. ScFvs can be used to facilitate phage display or can be used for flow cytometry, immunohistochemistry, or as targeting domains. Methods of making and using scFvs are known in the art. ScFvs may also be conjugated to a human constant domain (e.g. a heavy constant domain is derived from an IgG do-main, such as lgG1 , lgG2, lgG3, or lgG4, or a heavy chain constant domain derived from IgA, IgM, or IgE). Diabodies, triabodies, and tetrabodies and higher order variants are typically created by varying the length of the linker peptide from zero to several amino acids. Alternatively, it is also well known in the art that multivalent binding antibody variants can be generated using self-assembling units linked to the variable domain.

[0015] A “single-domain antibody” refers to an antibody fragment consisting of a single, monomeric variable antibody domain.

[0016] Multi-specific antibodies include bi-specific antibodies, tri-specific, or anti-bodies of four or more specificities. Multi-specific antibodies may be created by combining the heavy and light chains of one antibody with the heavy and light chains of one or more other antibodies. These chains can be covalently linked.

[0017] An antibody of the disclosure may be a Dual-affinity Re-targeting Antibody (DART). The DART format is based on the diabody format that separates cognate variable domains of heavy and light chains of the 2 antigen binding specificities on 2 separate polypeptide chains. Whereas the 2 polypeptide chains associate noncovalently in the diabody format, the DART format provides additional stabilization through a C-terminal disulfide bridge. DARTs can be produced in high quantity and quality and reveal exceptional stability in both formulation buffer and human serum.

[0018] As used herein "Monoclonal antibody" refers to an antibody that is derived from a single copy or clone, including e.g., any eukaryotic, prokaryotic, or phage clone. "Monoclonal antibody" is not limited to antibodies produced through hybridoma technology. Monoclonal antibodies can be produced using hybridoma techniques well known in the art, as well as recombinant technologies, phage display technologies, synthetic technologies or combinations of such technologies and other technologies readily known in the art. Furthermore, the monoclonal antibody may be labeled with a detectable label, immobilized on a solid phase and/or conjugated with a heterologous compound (e.g., an enzyme or toxin) according to methods known in the art.

[0019] As used herein “heavy chain antibody” refers to an antibody that consists of two heavy chains. A heavy chain antibody may be an IgG-like antibody from camels, llamas, alpacas, sharks, etc., or an IgNAR from a cartiliaginous fish.

[0020] As used herein "humanized antibody" refers to a non-human antibody that has been modified to reduce the risk of the non-human antibody eliciting an immune response in humans following administration but retains similar binding specificity and affinity as the starting non-human antibody. A humanized antibody binds to the same or similar epitope as the non-human antibody. The term “humanized antibody” includes an antibody that is composed partially or fully of amino acid sequences derived from a human antibody germ line by altering the sequence of an antibody having non-human hypervariable regions (“HVR”). The simplest such alteration may consist simply of substituting the constant region of a human antibody for the murine constant region, thus resulting in a human/murine chimera which may have sufficiently low immunogenicity to be acceptable for pharmaceutical use. Preferably, the variable region of the antibody is also humanized by techniques that are by now well known in the art. For example, the framework regions of a variable region can be substituted by the corresponding human framework regions, while retaining one, several, or all six non-human HVRs. Some framework residues can be substituted with corresponding residues from a non-human VL domain or VH domain (e.g., the non- human antibody from which the HVR residues are derived), e.g., to restore or improve specificity or affinity of the humanized antibody. Substantially human framework regions have at least about 75% homology with a known human framework sequence (i.e. at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% sequence identity). HVRs may also be randomly mutated such that binding activity and affinity for the antigen is maintained or enhanced in the context of fully human germ line framework regions or framework regions that are substantially human. As mentioned above, it is sufficient for use in the methods of this discovery to employ an antibody fragment. Further, as used herein, the term "humanized antibody" refers to an antibody comprising a substantially human framework region, at least one HVR from a nonhuman antibody, and in which any constant region present is substantially human. Substantially human constant regions have at least about 90% with a known human constant sequence (i.e. about 90%, about 95%, or about 99% sequence identity). Hence, all parts of a humanized antibody, except possibly the HVRs, are substantially identical to corresponding pairs of one or more germline human immunoglobulin sequences.

[0021 ] If desired, the design of humanized immunoglobulins may be carried out as follows or using similar methods familiar to those with skill in the art (for example, see Almagro, et al. Front. Biosci. 2008, 13(5): 1619-33). A murine antibody variable region is aligned to the most similar human germline sequences (e.g. by using BLAST or similar algorithm). The CDR residues from the murine antibody sequence are grafted into the similar human “acceptor” germ line. Subsequently, one or more positions near the CDRs or within the framework (e.g., Vernier positions) may be reverted to the original murine amino acid in order to achieve a humanized antibody with similar binding affinity to the original murine antibody. Typically, several versions of humanized antibodies with different re-version mutations are generated and empirically tested for activity. The humanized antibody variant with properties most similar to the parent murine antibody and the fewest murine framework reversions is selected as the final humanized antibody candidate.

[0022] The term “specifically binds,” as used herein with regards to epitope binding agents, means that an epitope binding agent does not cross react to a significant extent with other epitopes on the protein of interest (e.g., MYCT1 ), or on other proteins in general.

[0023] The terms “Myc Target 1”, “MYC Target Protein 1”, “MTLC”, “Myc Target In Myeloid Cells Protein 1 ” or “MYCT1” encompasses all MYCT isoforms and orthologs, whether full-length, truncated, or post-translationally modified. In many animals, including but not limited to humans, non-human primates, rodents, fish, cattle, frogs, goats, and chicken, MYCT1 is encoded by the gene Myctl gene (aka FLJ21269 and MTLC). The gene encoding MYCT1 is located on chromosome 6 (band q25.2; chromosome location (bp) 152697895 - 152724567) in humans. MYCT1 was initially identified as a novel target of the c-Myc oncogene in myeloid cells. Previous reports have suggested overexpression in cancer cells can promote apoptosis, alteration of morphology, enhancement of anchorage-independent cell growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. MYCT1 was initially thought to be a transcription factor and binds to the promoters of several c-Myc-regulated genes and it has been suggested that the phenotypes seen in MYCT1 -overexpressing cells are a result of the deregulation of these genes. In humans, MYCT1 protein has two isoforms, isoform 1 which has a sequence of 235 amino acids in length, and a shorter isoform 2 which has a sequence of 187 amino acids in length. The amino acids 1 -19 of mouse MYCT1 is identical to amino acids 48-67 of human MYCT1 isoform 1 (FIG. 1A) and amino acids 1 -19 of human MYCT1 isoform 2. [0024] In an exemplary aspect, a full length MYCT1 polypeptide human isoform 1 comprises the amino acid sequence of SEQ ID NO: 145 MRTQVYEGLCKNYFSLAVLQRDRIKLLFFDILVFLSVFLLFLLFLVDIMANNTTSLGSPW PENFWEDLIMSFTVSMAIGLVLGGFIWAVFICLSRRRRASAPISQWSSSRRSRSSYTHG LNRTGFYRHSGCERRSNLSLASLTFQRQASLEQANSFPRKSSFRASTFHPFLQCPPLP VETESQLVTLPSSNISPTISTSHSLSRPDYWSSNSLRVGLSTPPPPAYESIIKAFPDS.

[0025] In some aspects, a MYCT1 polypeptide human isoform 2, comprises the amino acid sequence of SEQ ID NO: 148 MANNTTSLGSPWPENFWEDLIMSFTVSMAIGLVLGGFIWAVFICLSRRRRASAPISQW SSSRRSRSSYTHGLNRTGFYRHSGCERRSNLSLASLTFQRQASLEQANSFPRKSSFR ASTFHPFLQCPPLPVETESQLVTLPSSNISPTISTSHSLSRPDYWSSNSLRVGLSTPPP PAYESIIKAFPDS.

[0026] In some aspects, a human MYCT1 polynucleotide comprises the nucleic acid sequence of SEQ ID NO: 149 ATGCGAACACAAGTATATGAGGGGTTGTGTAAAAATTATTTTTCTCTTGCTGTACTA CAAAGAGATAGAATCAAACTGCTTTTTTTCGACATACTGGTTTTTCTTTCTGTTTTTC TTCTCTTTCTTCTATTTCTTGTGGATATTATGGCTAATAACACAACAAGTTTAGGGAG TCCATGGCCAGAAAACTTTTGGGAGGACCTTATCATGTCCTTCACTGTATCCATGG CAATCGGGCTGGTACTTGGAGGATTTATTTGGGCTGTGTTCATTTGTCTGTCTCGA AGAAGAAGAGCCAGTGCTCCCATCTCACAGTGGAGTTCAAGCAGGAGATCTAGGT CTTCTTACACCCACGGCCTCAACAGAACTGGATTTTACCGCCACAGTGGCTGTGAA CGTCGAAGCAACCTCAGCCTGGCCAGTCTCACCTTCCAGCGACAAGCTTCCCTGG AACAAGCAAATTCCTTTCCAAGAAAATCAAGTTTCAGAGCTTCTACTTTCCATCCCT TTCTGCAATGTCCACCACTTCCTGTGGAAACTGAGAGTCAGCTGGTGACTCTCCCT TCTTCCAATATCTCTCCCACCATCAGCACTTCCCACAGTCTGAGCCGTCCTGACTA CTGGTCCAGTAACAGTCTTCGAGTGGGCCTTTCAACACCGCCCCCACCTGCCTAT GAGTCCATCATCAAGGCATTCCCAGATTCCTGA

[0027] In some aspects, the mouse MYCT1 polypeptide comprises the sequence of SEQ ID NO: 150 MANNTTSLGSPWPENFWEDLIMSFTVSVAIGLAIGGFLWALFVFLSRRRRASAPISQW SPTRRPRSSYNHGLNRTGFYRHSGYERRSNLSLASLTFQRQASMELVNSFPRKSSFR ASTFHPFLQCPPLPVETESQLMTLSASTTPSTLSTAHSPSRPDFRWSSNSLRMGLSTP PPPAYESIIKAFPDS

[0028] In an exemplary aspect, a full length MYCT1 mRNA transcript, which is 3030 base pairs in length includes the NCBI Reference Sequence: NM_025107.3. Additional reference MYCT1 mRNAs include but are not limited to NM_001371624.1 NM_001371625.1 NM_001371626.1 NM_025107.3. In an exemplary aspect, regulatory elements which modulate the expression of MYCT1 include those described herein and those disclosed in Gene Card ID: GC06P152697.

[0029] The “percent identity” of two amino acid sequences can be determined using the algorithm of Karlin and Altschul Proc. Natl. Acad. Sci. USA 87:2264-68, 1990, modified as in Karlin and Altschul Proc. Natl. Acad. Sci. USA 90:5873-77, 1993. Such an algorithm is incorporated into the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. J. Mol. Biol. 215:403-10, 1990. BLAST protein searches can be performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to the protein molecules of interest. Where gaps exist between two sequences, Gapped BLAST can be utilized as described in Altschul et al., Nucleic Acids Res. 25(17):3389-3402, 1997. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

[0030] As used herein "nucleic acid”, "nucleic acid molecule”, and "polynucleotide” are used interchangeably herein. The terms “nucleic acid encoding . . .”, or “nucleic acid molecule encoding . . . ”, should be understood as referring to the sequence of nucleotides which encodes a polypeptide.

[0031 ] A polynucleotide described herein may comprise one or more nucleic acids each encoding a polypeptide, all operably linked to (i.e., in a functional relationship with) one or more regulatory sequences, such as a promoter. Such a polynucleotide may alternatively be referred to herein as a "nucleic acid construct” or "construct”. [0032] As used herein “polypeptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues.

[0033] Each amino acid sequence described herein by virtue of its identity or similarity percentage with a given amino acid sequence respectively has in a further preferred aspect an identity or a similarity of at least 60%, at least 61 %, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71 %, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81 %, at least 82%, at least 83%, at least 84%, 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% or 100% with the given nucleotide or amino acid sequence, respectively. The terms “homology”, “sequence identity” and the like are used interchangeably herein. Sequence identity is described herein as a relationship between two or more amino acid (polypeptide or protein) sequences or two or more nucleic acid (polynucleotide) sequences, as determined by comparing the sequences. In a preferred aspect, sequence identity is calculated based on the full length (in amino acids or nucleotides) of two given SEQ ID NOS or based on a portion thereof. A portion of a full-length sequence may be referred to as a fragment, and preferably means at least 50%, 60%, 70%, 80%, 90%, or 100% of the length (in amino acids or nucleotides) of a reference sequence. "Identity" also refers to the degree of sequence relatedness between two amino acid sequences, or between two nucleic acid sequences, as the case may be, as determined by the match between strings of such sequences. The degree of sequence identity between two sequences can be determined, for example, by comparing the two sequences using computer programs commonly employed for this purpose, such as global or local alignment algorithms. Non-limiting examples include BLASTp, BLASTn, Clustal W, MAFFT, Clustal Omega, AlignMe, Praline, GAP, BESTFIT, or another suitable method or algorithm. A Needleman and Wunsch global alignment algorithm can be used to align two sequences over their entire length or part thereof (part thereof may mean at least 50%, 60%, 70%, 80%, 90% of the length of this sequence), maximizing the number of matches and minimizes the number of gaps. Default settings can be used and preferred program is Needle for pairwise alignment (in an aspect, EMBOSS Needle 6.6.0.0, gap open penalty 10, gap extent penalty: 0.5, end gap penalty: false, end gap open penalty: 10 , end gap extent penalty: 0.5 is used) and MAFFT for multiple sequence alignment ( in an aspect, MAFFT v7Default value is: BLOSUM62 [bl62], Gap Open: 1.53, Gap extension: 0.123, Order: aligned , Tree rebuilding number: 2, Guide tree output: ON [true], Max iterate: 2 , Perform FFTS: none is used).

[0034] "Similarity" between two amino acid sequences is determined, for example, by comparing the amino acid sequence and its conserved amino acid substitutes of one polypeptide to the sequence of a second polypeptide. Similar algorithms used for determination of sequence identity may be used for determination of sequence similarity. Optionally, in determining the degree of amino acid similarity, the skilled person may also take into account so-called conservative amino acid substitutions. As used herein, “conservative” amino acid substitutions refer to the interchangeability of residues having similar side chains. Examples of classes of amino acid residues for conservative substitutions are given in the Tables below:

Alternative conservative amino acid residue substitution classes :

Alternative physical and functional classifications of amino acid residues:

[0035] For example, a group of amino acids having aliphatic side chains is glycine, alanine, valine, leucine, and isoleucine; a group of amino acids having aliphatic- hydroxyl side chains is serine and threonine; a group of amino acids having am ide- containing side chains is asparagine and glutamine; a group of amino acids having aromatic side chains is phenylalanine, tyrosine, and tryptophan; a group of amino acids having basic side chains is lysine, arginine, and histidine; and a group of amino acids having sulphur-containing side chains is cysteine and methionine. Preferred conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, and asparagine-glutamine. Substitutional variants of the amino acid sequence disclosed herein are those in which at least one residue in the disclosed sequences has been removed and a different residue inserted in its place. Preferably, the amino acid change is conservative. Preferred conservative substitutions for each of the naturally occurring amino acids are as follows: Ala to Ser; Arg to Lys; Asn to Gin or His; Asp to Glu; Cys to Ser or Ala; Gin to Asn; Glu to Asp; Gly to Pro; His to Asn or Gin; lie to Leu or Vai; Leu to He or Vai; Lys to Arg; Gin or Glu; Met to Leu or He; Phe to Met, Leu or Tyr; Ser to Thr; Thr to Ser; Trp to Tyr; Tyr to Trp or Phe; and, Vai to He or Leu.

[0036] As used herein "fragment" means a portion of a polypeptide that contains, preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or more of the entire length of the reference polypeptide. In certain aspects, the fragment as the same or similar biological activity as the reference polypeptide.

[0037] The terms “treat,” "treating," or "treatment" as used herein, refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological change or disease/disorder. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e. , not worsening) state of disease, a delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. Those in need of treatment include those already with the disease, condition, or disorder as well as those prone to have the disease, condition or disorder or those in which the disease, condition or disorder is to be prevented.

[0038] As used herein “cancer,” “tumor,” or “malignancy” may refer to one or more neoplasm or cancer. The neoplasm may be malignant or benign, the cancer may be primary or metastatic; the neoplasm or cancer may be early stage or late stage. Non-limiting examples of neoplasms or cancers may include acute lymphoblastic leukemia, acute myeloid leukemia, adrenocortical carcinoma, AIDS-related cancers, AIDS-related lymphoma, anal cancer, appendix cancer, astrocytomas (childhood cerebellar or cerebral), basal cell carcinoma, bile duct cancer, bladder cancer, bone cancer, brainstem glioma, brain tumors (cerebellar astrocytoma, cerebral astrocytoma/malignant glioma, ependymoma, medulloblastoma, supratentorial primitive neuroectodermal tumors, visual pathway and hypothalamic gliomas), breast cancer, bronchial adenomas/carcinoids, Burkitt lymphoma, carcinoid tumors (childhood, gastrointestinal), carcinoma of unknown primary, central nervous system lymphoma (primary), cerebellar astrocytoma, cerebral astrocytoma/malignant glioma, cervical cancer, childhood cancers, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorders, colon cancer, cutaneous T-cell lymphoma, desmoplastic small round cell tumor, endometrial cancer, ependymoma, esophageal cancer, Ewing's sarcoma in the Ewing family of tumors, extracranial germ cell tumor (childhood), extragonadal germ cell tumor, extrahepatic bile duct cancer, eye cancers (intraocular melanoma, retinoblastoma), gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, germ cell tumors (childhood extracranial, extragonadal, ovarian), gestational trophoblastic tumor, gliomas (adult, childhood brain stem, childhood cerebral astrocytoma, childhood visual pathway and hypothalamic), gastric carcinoid, hairy cell leukemia, head and neck cancer, hepatocellular (liver) cancer, Hodgkin lymphoma, hypopharyngeal cancer, hypothalamic and visual pathway glioma (childhood), intraocular melanoma, islet cell carcinoma, Kaposi sarcoma, kidney cancer (renal cell cancer), laryngeal cancer, leukemias (acute lymphoblastic, acute myeloid, chronic lymphocytic, chronic myelogenous, hairy cell), lip and oral cavity cancer, liver cancer (primary), lung cancers (non-small cell, small cell), lymphomas (AIDS-related, Burkitt, cutaneous T-cell, Hodgkin, non-Hodgkin, primary central nervous system), macroglobulinemia (Waldenstrom), malignant fibrous histiocytoma of bone/osteosarcoma, medulloblastoma (childhood), melanoma, intraocular melanoma, Merkel cell carcinoma, mesotheliomas (adult malignant, childhood), metastatic squamous neck cancer with occult primary, mouth cancer, multiple endocrine neoplasia syndrome (childhood), multiple myeloma/plasma cell neoplasm, mycosis fungoides, myelodysplastic syndromes, myelodysplastic/myeloproliferative diseases, myelogenous leukemia (chronic), myeloid leukemias (adult acute, childhood acute), multiple myeloma, myeloproliferative disorders (chronic), nasal cavity and paranasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer, oral cancer, oropharyngeal cancer, osteosarcoma/malignant fibrous histiocytoma of bone, ovarian cancer, ovarian epithelial cancer (surface epithelial-stromal tumor), ovarian germ cell tumor, ovarian low malignant potential tumor, pancreatic cancer, pancreatic cancer (islet cell), paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineal astrocytoma, pineal germinoma, pineoblastoma and supratentorial primitive neuroectodermal tumors (childhood), pituitary adenoma, plasma cell neoplasia, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell carcinoma (kidney cancer), renal pelvis and ureter transitional cell cancer, retinoblastoma, rhabdomyosarcoma (childhood), salivary gland cancer, sarcoma (Ewing family of tumors, Kaposi, soft tissue, uterine), Sezary syndrome, skin cancers (nonmelanoma, melanoma), skin carcinoma (Merkel cell), small cell lung cancer, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma, squamous neck cancer with occult primary (metastatic), stomach cancer, supratentorial primitive neuroectodermal tumor (childhood), T-Cell lymphoma (cutaneous), testicular cancer, throat cancer, thymoma (childhood), thymoma and thymic carcinoma, thyroid cancer, thyroid cancer (childhood), transitional cell cancer of the renal pelvis and ureter, trophoblastic tumor (gestational), unknown primary site (adult, childhood), ureter and renal pelvis transitional cell cancer, urethral cancer, uterine cancer (endometrial), uterine sarcoma, vaginal cancer, visual pathway and hypothalamic glioma (childhood), vulvar cancer, Waldenstrom macroglobulinemia, and Wilms tumor (childhood).

[0039] As used herein, treatment of cancer can comprise increased inhibition of cancer progression and/or metastases, inhibition of an increase in tumor volume, a reduction in tumor volume and/or growth, a reduction in tumor growth rate, an eradication or killing of a tumor and/or cancer cell, or any combination thereof. In some aspects, the treatment can also prolong the survival of a subject, improve the prognosis and/or improve the quality of life of the subject. [0040] As used herein “resistant” or “insensitive” cancers, tumor cells, and tumors refers to cancers that have become resistant to cancer therapy (for e.g., immune checkpoint inhibitor) and may lead to increased tumor volume, cancer metastasis, cancer recurrence, or decreased life expectancy.

[0041 ] A subject may be a rodent, a human, a livestock animal, a companion animal, or a zoological animal. In one aspects, the subject may be a rodent, e.g. a mouse, a rat, a guinea pig, etc. In another aspects the subject may be a livestock animal. Non-limiting examples of suitable livestock animals may include pigs, cows, horses, goats, sheep, llamas and alpacas. In still another aspect, the subject may be a companion animal. Non-limiting examples of companion animals may include pets such as dogs, cats, rabbits, and birds. In yet another aspect, the subject may be a zoological animal. As used herein, a “zoological animal” refers to an animal that may be found in a zoo. Such animals may include non-human primates, large cats, wolves, and bears. In a preferred aspect, the subject is a human.

[0042] As used herein “control sample” or “control cell” can be procured from a healthy subject and/or a subject with cancer procured prior to the start of treatment (baseline). A control subject is a healthy subject, or a subject not receiving treatment. In some aspects, the parameters measured during treatment can be an average of several control subjects, or a population average. In some aspects, the control sample can comprise of non-cancer cells. In some aspects, the non-cancer cells can be from the same tissue type as the cancer cells. For example, if the cancer cells are from breast cancer, then the non-cancer cells can be from healthy breast tissue. In some aspects, the control can comprise of an average levels of the analyte in a sample from a subject before onset of cancer. In some aspects, control sample can be a sample from the subject prior to diagnosis or treatment. In certain aspects, the analyte can be measured in a person or persons other than the subject with cancer. In some aspects, the control a person or persons with similar characteristics to the subject with cancer. In some aspects, the control can be an average of the combination of disclosed analyte levels from different healthy sources (e.g., more than one healthy control subject and/or more than one subject prior to the start of treatment (baseline)). In some aspects, the control sample can be pooled sample.

[0043] As used herein, a biological sample may be of any biological tissue, fluid, or cell from the subject. The sample can be solid or fluid. The sample can be a heterogeneous cell population. Non-limiting examples of suitable biological samples include sputum, serum, blood, blood cells (e.g., white cells), a biopsy, urine, peritoneal fluid, pleural fluid, or cells derived therefrom. The biopsy can be a fine needle aspirate biopsy, a core needle biopsy, a vacuum assisted biopsy, an open surgical biopsy, a shave biopsy, a punch biopsy, an incisional biopsy, a curettage biopsy, or a deep shave biopsy. Biological samples may also include sections of tissues, such as frozen sections or formalin fixed sections taken for histological purposes. A sample can be a tumor tissue, tissue surrounding a tumor, or non-tumor tissue. Methods of procuring a biological sample from a subject are well known in the art.

[0044] As used herein, the term "vector" is understood as a nucleic acid means which includes a nucleotide sequence that can be introduced into a host cell to be recombined and inserted into the genome of the host cell, or spontaneously replicated as an episome. The vector may include linear nucleic acids, plasmids, phagemids, cosmids, RNA vectors, virus vectors, and analogs thereof. Examples of the virus vectors may include retroviruses, adenoviruses, and adeno-associated viruses, but are not limited thereto.

[0045] As used herein “immune checkpoint inhibitor” or “ICI” is a drug that blocks immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly for e.g. cancer. Immune checkpoint inhibitors work by preventing cancer cells from turning T-cells (white blood cells that detect infections and abnormalities) off. Non-limiting examples of immune checkpoint inhibitors include inhibitors of PD-1 , PD-L1 , TIM-3, LAG- 3, CTLA-4, and CSF- 1 R and any combination thereof. The immune checkpoint receptors may be on tumor cells or immune cells such as T cells, monocytes, microglia, and macrophages, without limitation. The agents which assert immune checkpoint blockade may be small chemical entities or polymers, antibodies, antibody fragments, single chain antibodies or other antibody constructs, including, but not limited to, bispecific antibodies and diabodies. Immune checkpoint inhibitors which may be used according to the disclosure include any that disrupt the inhibitory interaction of cytotoxic T cells and tumor cells. These include but are not limited to anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA4 antibody, anti-LAG-3 antibody, anti-TIM-3 antibody. The inhibitor need not be an antibody but can be a small molecule or other polymer. If the inhibitor is an antibody it can be a polyclonal, monoclonal, fragment, single chain, or other antibody variant construct. Inhibitors may target any immune checkpoint known in the art, including but not limited to, CTLA-4, PDL1 , PDL2, PD1 , B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, CSF-1 R, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK1 , CHK2, A2aR, CD28, CD86, CD69, CD48, CD113, CEACAM-1 , Galectin-1 , TIGIT, GPR56, CD48, GARP, PD1 H, LAIR1 , TIM1 , TIM4 and the B-7 family of ligands. Combinations of inhibitors for a single target immune checkpoint or different inhibitors for different immune checkpoints may be used. Illustrative examples of immune checkpoint inhibitors include CTLA-4 blocking antibodies (Ipilimumab (Yervoy), Tremelimumab (Imjuno)), PD-1 inhibitors (Pembrolizumab (Keytruda), Nivolumab (Opdivo), Cemiplimab (Libtayo), CT- 011 (Pidilizumab), AMP224), PD-L1 inhibitors (Atezolizumab (tecentriq), Avelumab (Bavencio), Durvalumab (Imfinzi), BMS- 936559), Lag3 inhibitors (Relatlimab), combination of Lag3 and PD1 inhibitor (PD-1 inhibitor nivolumab (Opdualag) 0X40 inhibitor (MEDI6469), CD160 inhibitor (BY55). Non-limiting examples of inhibitors of CSF-1 R include PLX3397, PLX486, RG7155, AMG820, ARRY-382, FPA008, IMC-CS4, JNJ-40346527, and MCS 110. The terms “ICI treatment”, ‘ ICI therapy”, “ICI compounds”, and the like, refer to one or more ICI (or the use thereof) disclosed herein or known to those of skill in the art.

[0046] As used herein “angiogenesis” is the growth of blood vessels from the existing vasculature. Angiogenesis can be further defined herein as involving: (i) activation of endothelial cells; (ii) increased vascular permeability; (iii) subsequent dissolution of the basement membrane and extravasation of plasma components leading to formation of a provisional fibrin gel extracellular matrix; (iv) proliferation and mobilization of endothelial cells; (v) reorganization of mobilized endothelial cells to form functional capillaries; (vi) capillary loop formation; (vi) deposition of basement membrane and recruitment of perivascular cells to newly formed vessels, or any combination thereof. Normal angiogenesis is active during tissue growth from embryonic development through maturity and then enters a period of relative quiescence during adulthood. Normal angiogenesis is also activated during wound healing, and at certain stages of the female reproductive cycle. Inappropriate or pathological angiogenesis has been associated with several disease states including various retinopathies, ischemic disease, atherosclerosis, chronic inflammatory disorders, and cancer. Pathological angiogenesis may be formation or neogenesis of blood vessels that are not in a physiologically normal state. Such blood vessels, being immature and diapedetic, may become blood vessels where the blood may not be perfused. Also, the pathological angiogenesis may be an angiogenesis or neovascularization in a manner different from a physiologically normal state. For example, the term may refer to formation of new blood vessels by receiving stimulus such as inflammation.

[0047] As used herein “disease or disorder related to angiogenesis” relates to any disease or disorder which generates the above-mentioned “pathological angiogenesis or neovascularization”, or causes an individual to malfunction due to “pathological angiogenesis or neovascularization”. Non-limiting examples of such a disease or disorder include, age-related macular degeneration, ischemic retinopathy, intraocular neovascularization, corneal neovascularization, retinal neovascularization, choroidal neovascularization, diabetic macular edema, diabetic retina ischemia, diabetic retinal edema, diabetic retinopathy, cancers, rheumatoid arthritis, endometriosis, and alopecia. In some aspects, the disease or disorder is cancer.

[0048] As used herein a “VEGF inhibitor” describe inhibitors of VEGF synthesis or activity, as the case may be, at the protein level, to prevent or downregulate the production of the protein, or at least one biological activity of the protein once produced. In some aspects, a VEGF inhibitor may be selected from the group consisting of: an anti-VEGF immunoglobulin, an anti-VEGF antibody, an anti- VEGF monoclonal antibody and a humanized anti-VEGF monoclonal antibody.

[0049] As used herein “formulation” refers to preparing a drug in a form suitable for administration to a subject, such as a human. Thus, a “formulation” can include pharmaceutically acceptable excipients, including diluents or carriers.

[0050] As used herein “pharmaceutically acceptable” describe substances or components that do not cause unacceptable losses of pharmacological activity or unacceptable adverse side effects. Examples of pharmaceutically acceptable ingredients can be those having monographs in United States Pharmacopeia (USP 29) and National Formulary (NF 24), United States Pharmacopeial Convention, Inc, Rockville, Maryland, 2005 (“USP/NF”), or a more recent edition, and the components listed in the continuously updated Inactive Ingredient Search online database of the FDA. Other useful components that are not described in the USP/NF, etc. may also be used.

[0051 ] As used herein “pharmaceutically acceptable excipient,” as used herein, can include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic, or absorption delaying agents. The use of such media and agents for pharmaceutical active substances is well known in the art (see generally Remington’s Pharmaceutical Sciences (A.R. Gennaro, Ed.), 21st edition, ISBN: 0781746736 (2005)). Except insofar as any conventional media or agent is incompatible with an active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions.

[0052] As used herein “stable” formulation or composition can refer to a composition having sufficient stability to allow storage at a convenient temperature, such as between about 0 °C and about 60 °C, for a commercially reasonable period of time, such as at least about one day, at least about one week, at least about one month, at least about three months, at least about six months, at least about one year, or at least about two years.

[0053] As used herein “expression” or “expression level” or “level of expression” refers to amount of a particular analyte (e.g., MYCT1 ) present in the sample. The amount may be a concentration, number, ratio, proportion, or a percentage of the analyte compared to the control sample or determined using a standard curve. The amount may be an absolute amount or a relative amount.

[0054] As used herein "combination therapy" refers to the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.

[0055] As used herein "therapeutically effective" or “effective” is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder or on the effecting of a clinical endpoint. An effective amount can be an amount which achieve an intended purpose. For example, an effective amount of antibody may be an amount that decreases tumor volume (e.g., shrinks or eliminates a tumor or reduces the number of circulating cancer cells). Determination of effective amounts is well within the capability of those skilled in the art, especially in light of the disclosure provided herein.

II. anti-MYCT1 antibodies

[0056] The present disclosure provides antibodies which specifically bind to MYCT1 protein. In some aspects, the antibody of the disclosure bind to an epitope of MYCT1 protein. In some aspects, the antibody described herein can be an isolated antibody that bind an epitope of MYCT1 protein. In some aspects, isolated antibody herein can bind an epitope of MYCT1 protein, wherein the MYCT1 protein is a human MYCT1 protein. In some aspects, isolated antibody herein can bind an epitope of MYCT1 protein, wherein the MYCT1 protein is a mouse MYCT1 protein.

[0057] In certain aspects, provided herein are antibodies that bind to extracellular domain of MYCT1 . In some aspects, provided herein is an antibody which specifically binds to an epitope within the first 150 amino acids of MYCT1 protein. In some aspects, the antibody binds to an epitope within the first 100 amino acids of MYCT1. In some aspects, the antibody binds to an epitope within the first 70 amino acids of MYCT1 . In some aspects, the antibody binds to an epitope within the first 67 amino acids of MYCT1 comprising the amino acid sequence of SEQ ID NO: 145. In some aspects, the antibody binds to an epitope within the first 30 amino acids of MYCT 1 comprising the amino acid sequence of SEQ ID NO: 148 or SEQ ID NO: 150. In some aspects, the antibody binds to an epitope within the first 20 amino acids of MYCT 1 comprising the amino acid sequence of SEQ ID NO: 148 or SEQ ID NO: 150. In some aspects the epitope comprises the amino acid sequence of SEQ ID NO: 146.

[0058] In certain aspects, antibodies described herein may have a suitable binding affinity for a target antigen e.g., a MYCT1 protein or an epitope thereof. As used herein, “binding affinity” refers to the apparent association constant or KA. The KA is the reciprocal of the dissociation constant (KD). In some aspects, an antibody described herein may have a binding affinity (KD) of at least about 100 nM, at least about 10 nM, at least about 1 nM, at least about 0.1 nM, or lower for a MYCT1 protein or an epitope thereof. In some aspects, an antibody described herein may have a binding affinity (KD) of between about 0.1 pM to about 10 pM, preferably about 0.1 pM to about 1 pM, more preferably about 0.1 pM to about 100 nM. In some aspects, an antibody described herein may have a binding affinity (KD) between about 100 nM to about 0.1 nM (e.g., about 100 nM, about 75 nM, about 50 nM, about 25 nM, about 10 nM, about 5 nM, about 1 nM, about 0.75 nM, about 0.5 nM, about 0.25 nM, about 0.1 nM) for a MYCT1 protein or an epitope thereof. In some aspects, an antibody described herein may have a binding affinity (KD) between about 50 nM to about 40 nM (e.g., about 50 nM, about 49 nM, about 48 nM, about 47 nM, about 46 nM, about 45 nM, about 44 nM, about 43 nM, about 42 nM, about 41 nM, about 40 nM) for a MYCT1 protein or an epitope thereof. In some aspects, an antibody described herein may have a binding affinity (KD) between about 50 nM to about 40 nM (e.g., about 50 nM, about 49 nM, about 48 nM, about 47 nM, about 46 nM, about 45 nM, about 44 nM, about 43 nM, about 42 nM, about 41 nM, about 40 nM) for a MYCT1 protein or an epitope thereof. In some aspects, binding affinity (or binding specificity) can be determined by a variety of methods including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance, and/or spectroscopy e.g., using a fluorescence assay).

[0059] In certain aspects, antibodies described herein may have neutralizing activity against MYCT1 protein. In some aspects, antibodies described herein may have neutralizing activity against MYCT1 protein with IC50 less than about 150 ng/mL. In some aspects, antibodies described herein may have neutralizing activity against MYCT1 protein with IC50 ranging from about 0.1 ng/ml to about 150 ng/mL (e.g., about 0.1 ng/ml, about 0.25 ng/ml, about 0.5 ng/ml, about 1 ng/ml, about 2.5 ng/ml, about 5 ng/ml, about 7.5 ng/ml, about 10 ng/ml, about 25 ng/ml, about 50 ng/ml, about 75 ng/ml, about 100 ng/ml, about 125 ng/ml, about 150 ng/ml).

[0060] In some aspects, antibodies described herein may decrease the expression and/or activity of MYCT1 compared to MYCT1 expression and/or activity in the absence of an antibody herein. In certain aspects, antibodies described herein may decrease MYCT1 expression and/or activity by about 5% to about 99% (e.g., about 5%, 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%, about 99%) compared to MYCT1 expression and/or activity in the absence of an antibody herein.

[0061 ] In some aspects, MYCT1 expression can be measured using known methods in the art. By way of non-limiting examples, expression levels of MYCT1 can be measured using RNA-seq, nanopore sequencing, Nanostring, multiplex RT-PCR, single-plex RT-PCR, NASBA, Fluorescence measurements or spectrophotometry. MYCT1 interacts with tight junction protein Zona Occludens 1 and regulated Rho GTPase-mediated actin cytoskeleton dynamics, thereby promoting endothelial cell motility. Accordingly, in certain aspects, actin cytoskeleton dynamics may be measured as an indication of MYCT1 activity. Actin cytoskeleton dynamics and MYCT1 activity may be measured using methods standard in the art as described below in the Examples. In still another aspect, tube-like structure formation in Matrigel assay, Boyden chamber tumor chemotaxis assay, wound-closure assay, and cell morphology assays may be measured as an indication of MYCT1 activity.

[0062] In certain aspects, antibodies described herein may have the same heavy chain CDRs, and/or light chain CDRs as any of the exemplary antibodies described herein (e.g., antibody clones 2B4, 9F8, 8D2). Two antibodies having the same heavy chain CDRs, and/or light chain CDRs means that their CDRs are identical when determined by the same approach (e.g., the Kabat approach, the Chothia approach, the AbM approach, the Contact approach, or the IMGT approach). In certain aspects, antibodies described herein may have the same heavy chain and/or light chain as any of the exemplary antibodies described herein. In certain embodiments, antibodies disclosed herein may share one or more amino acid sequences provided in Table 7.

[0063] In some aspects, antibodies herein may comprise heavy chains that are at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) sequence identity, individually or collectively, as compared with the heavy chain of an exemplary antibody described herein. In some aspects, antibodies herein may comprise light chains that are at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) sequence identity, individually or collectively, as compared with the light chains of an exemplary antibody described herein. In some aspects, antibodies herein may comprise heavy chain CDRs that are at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) sequence identity, individually or collectively, as compared with the heavy chain CDRs of an exemplary antibody described herein. In some aspects, antibodies herein may comprise light chain CDRs that are at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) sequence identity, individually or collectively, as compared with the light chain CDRs of an exemplary antibody described herein.

[0064] In some aspects, isolated anti-MYCT1 antibodies may comprise a heavy chain variable region (VH) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 18, 54, 90 or 126. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 18. In some aspects, the anti- MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 54. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 90. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 126.

[0065] In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the amino acid sequence of any one of SEQ ID NOs: 18, 54, 90 or 126. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the amino acid sequence of SEQ ID NO: 18. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the amino acid sequence of SEQ ID NO: 54. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the amino acid sequence of SEQ ID NO: 90. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the amino acid sequence of SEQ ID NO: 126.

[0066] In some aspects, isolated anti-MYCT1 antibodies may comprise a light chain variable region (VL) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 36, 72, 108 or 144. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 36. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 72. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 108. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 144.

[0067] In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the amino acid sequence of any one of SEQ ID NOs: 36, 72, 108 or 144. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the amino acid sequence of SEQ ID NO: 36. In some aspects, isolated anti- MYCT 1 antibodies may comprise a VL that comprises the amino acid sequence of SEQ ID NO: 72. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the amino acid sequence of SEQ ID NO: 108. In some aspects, isolated anti- MYCT 1 antibodies may comprise a VL that comprises the amino acid sequence of SEQ ID NO: 144.

[0068] In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 18, 54, 90 or 126; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 36, 72, 108 or 144, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 18; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 36. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 54; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 72. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 90; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 108. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 126; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 144.

[0069] In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the amino acid sequence of any one of SEQ ID NOs: 18, 54, 90 or 126; and a VL that comprises the amino acid sequence of any one of SEQ ID NOs: 36, 72, 108 or 144, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the amino acid sequence of SEQ ID NO: 18; and a VL that comprises the sequence of SEQ ID NO: 36. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the amino acid sequence of SEQ ID NO: 54; and a VL that comprises the amino acid sequence of SEQ ID NO: 72. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the sequence of SEQ ID NO: 90; and a VL that comprises the amino acid sequence of SEQ ID NO: 108. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the amino acid sequence of SEQ ID NO: 126; and a VL that comprises the amino acid sequence of SEQ ID NO: 144.

[0070] In some aspects, isolated anti-MYCT1 antibodies may comprise a heavy chain variable region 1 (H1 ) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 10. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 46. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 82. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 118.

[0071 ] In some aspects, isolated anti-MYCT1 antibodies may comprise a heavy chain variable region 1 (H1 ) that comprises the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the amino acid sequence of SEQ ID NOs: 10. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the amino acid sequence of SEQ ID NOs: 46. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the amino acid sequence of SEQ ID NOs: 82. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the amino acid sequence of SEQ ID NOs: 118.

[0072] In some aspects, isolated anti-MYCT1 antibodies may comprise a light chain variable region 1 (L1 ) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100 or 136. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 28. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 64. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 100. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 136.

[0073] In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100 or 136. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 28. In some aspects, isolated anti- MYCT1 antibodies may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 64. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 100. In some aspects, isolated anti- MYCT1 antibodies may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 136.

[0074] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100 or 136, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 10; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 28. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 46; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 64. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 82; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 100. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 118; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 136.

[0075] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118; and a L1 that comprises the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100 or 136, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 10; and a L1 that comprises the amino acid sequence of SEQ ID NO: 28. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 46; and a L1 that comprises the amino acid sequence of SEQ ID NO: 64. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 82; and a L1 that comprises the amino acid sequence of SEQ ID NO: 100. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the sequence of SEQ ID NO: 118; and a L1 that comprises the amino acid sequence of SEQ ID NO: 136.

[0076] In some aspects, isolated anti-MYCT1 antibodies may comprise a heavy chain variable region 2 (H2) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 12. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 48. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 84. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NOs: 120.

[0077] In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 12. In some aspects, isolated anti- MYCT1 antibodies may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 48. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 84. In some aspects, isolated anti- MYCT1 antibodies may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 120.

[0078] In some aspects, isolated anti-MYCT1 antibodies may comprise a light chain variable region 2 (L2) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102 or 138. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 30. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 66. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 102. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 138.

[0079] In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102 or 138. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the amino acid sequence of SEQ ID NO: 30. In some aspects, isolated anti- MYCT1 antibodies may comprise a L2 that comprises the amino acid sequence of SEQ ID NO: 66. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the amino acid sequence of SEQ ID NO: 102. In some aspects, isolated anti- MYCT1 antibodies may comprise a L2 that comprises the amino acid sequence of SEQ ID NO: 138.

[0080] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102 or 138, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 12; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 30. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 48; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 66. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 84; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 102. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 120; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 138.

[0081 ] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120; and a L2 that comprises the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102 or 138, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 12; and a L2 that comprises the amino acid sequence of SEQ ID NO: 30. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the sequence of SEQ ID NO: 48; and a L2 that comprises the amino acid sequence of SEQ ID NO: 66. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 84; and a L2 that comprises the sequence of SEQ ID NO: 102. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H2 that comprises the amino acid sequence of SEQ ID NO: 120; and a L2 that comprises the amino acid sequence of SEQ ID NO: 138.

[0082] In some aspects, isolated anti-MYCT1 antibodies may comprise a heavy chain variable region 3 (H3) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 14. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 50. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 86. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NOs: 122.

[0083] In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 14. In some aspects, isolated anti- MYCT1 antibodies may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 50. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 86. In some aspects, isolated anti- MYCT1 antibodies may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 122.

[0084] In some aspects, isolated anti-MYCT1 antibodies may comprise a light chain variable region 3 (L3) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104 or 140. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 32. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 68. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 104. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 140.

[0085] In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104 or 140. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the amino acid sequence of SEQ ID NO: 32. In some aspects, isolated anti- MYCT1 antibodies may comprise a L3 that comprises the amino acid sequence of SEQ ID NO: 68. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the amino acid sequence of SEQ ID NO: 104. In some aspects, isolated anti- MYCT1 antibodies may comprise a L3 that comprises the amino acid sequence of SEQ ID NO: 140.

[0086] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104 or 140, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 14; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 32. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 50; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 68. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 86; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 104. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 122; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 140.

[0087] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122; and a L3 that comprises the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104 or 140, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 14; and a L3 that comprises the sequence of SEQ ID NO: 32. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 50; and a L3 that comprises the amino acid sequence of SEQ ID NO: 68. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 86; and a L3 that comprises the amino acid sequence of SEQ ID NO: 104. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the amino acid sequence of SEQ ID NO: 122; and a L3 that comprises the amino acid sequence of SEQ ID NO: 140. [0088] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 10; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 12; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 14, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 46; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 48; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 50, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 82; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 84; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 86, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 118; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 120; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 122, or any combination thereof.

[0089] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118; a H2 that comprises the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120; and a H3 that comprises the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 10; a H2 that comprises the amino acid sequence of SEQ ID NO: 12; and a H3 that comprises the amino acid sequence of SEQ ID NO: 14, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 46; a H2 that comprises the amino acid sequence of SEQ ID NO: 48; and a H3 that comprises the amino acid sequence of SEQ ID NO: 50, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 82; a H2 that comprises the amino acid sequence of SEQ ID NO: 84; and a H3 that comprises the amino acid sequence of SEQ ID NO: 86, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 118; a H2 that comprises the amino acid sequence of SEQ ID NO: 120; and a H3 that comprises the amino acid sequence of SEQ ID NO: 122, or any combination thereof.

[0090] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100, or 136; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102, or 138; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104, or 140, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 28; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 30; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 32, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 64; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 66; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 68, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 100; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 102; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 104, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 136; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 138; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 140, or any combination thereof.

[0091 ] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100, or 136; a L2 that comprises the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102, or 138; and a L3 that comprises the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104, or 140, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 28; a L2 that comprises the amino acid sequence of SEQ ID NO: 30; and a L3 that comprises the amino acid sequence of SEQ ID NO: 32, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 64; a L2 that comprises the sequence of SEQ ID NO: 66; and a L3 that comprises the amino acid sequence of SEQ ID NO: 68, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 100; a L2 that comprises the sequence of SEQ ID NO: 102; and a L3 that comprises the amino acid sequence of SEQ ID NO: 104, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the amino acid sequence of SEQ ID NO: 136; a L2 that comprises the sequence of SEQ ID NO: 138; and a L3 that comprises the amino acid sequence of SEQ ID NO: 140, or any combination thereof.

[0092] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100, or 136; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102, or 138; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104, or 140, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 10; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 12; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NO: 14; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 28; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 30; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 32, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 46; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 48; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NO: 50; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 64; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 66; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 68, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 82; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 84; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NO: 86; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 100; a L2 that comprises at least about 80% (e g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 102; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 104, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 118; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 120; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of any one of SEQ ID NO: 122; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 136; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 138; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the amino acid sequence of SEQ ID NO: 140, or any combination thereof.

[0093] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of any one of SEQ ID NOs: 10, 46, 82, or 118; a H2 that comprises the amino acid sequence of any one of SEQ ID NOs: 12, 48, 84, or 120; a H3 that comprises the amino acid sequence of any one of SEQ ID NOs: 14, 50, 86, or 122; a L1 that comprises the amino acid sequence of any one of SEQ ID NOs: 28, 64, 100, or 136; a L2 that comprises the amino acid sequence of any one of SEQ ID NOs: 30, 66, 102, or 138; and a L3 that comprises the amino acid sequence of any one of SEQ ID NOs: 32, 68, 104, or 140, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 10; a H2 that comprises the amino acid sequence of SEQ ID NO: 12; a H3 that comprises the amino acid sequence of any one of SEQ ID NO: 14; a L1 that comprises the amino acid sequence of SEQ ID NO: 28; a L2 that comprises the sequence of SEQ ID NO: 30; and a L3 that comprises the sequence of SEQ ID NO: 32, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 46; a H2 that comprises the amino acid sequence of SEQ ID NO: 48; a H3 that comprises the sequence of any one of SEQ ID NO: 50; a L1 that comprises the amino acid sequence of SEQ ID NO: 64; a L2 that comprises the sequence of SEQ ID NO: 66; and a L3 that comprises the amino acid sequence of SEQ ID NO: 68, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 82; a H2 that comprises the sequence of SEQ ID NO: 84; a H3 that comprises the amino acid sequence of any one of SEQ ID NO: 86; a L1 that comprises the sequence of SEQ ID NO: 100; a L2 that comprises the amino acid sequence of SEQ ID NO: 102; and a L3 that comprises the amino acid sequence of SEQ ID NO: 104, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the amino acid sequence of SEQ ID NO: 118; a H2 that comprises the amino acid sequence of SEQ ID NO: 120; a H3 that comprises the amino acid sequence of any one of SEQ ID NO: 122; a L1 that comprises the amino acid sequence of SEQ ID NO: 136; a L2 that comprises the amino acid sequence of SEQ ID NO: 138; and a L3 that comprises the amino acid sequence of SEQ ID NO: 140, or any combination thereof.

[0094] In another exemplary aspect, the anti-MYCT1 antibody is one or more antibodies listed in Table 1.

Table 1 : Exemplary anti-MYCT1 antibodies [0095] In certain aspects, the heavy chain of any of the antibodies disclosed herein may further comprise a heavy chain constant region (CH) or a portion thereof (e.g., CH1 , CH2, CH3, or a combination thereof). In some aspects, a heavy chain constant region for use herein may be of any suitable origin, e.g., human, mouse, rat, or rabbit. In some aspects, alternatively or in addition, a light chain of any of the antibodies disclosed herein may further comprise a light chain constant region (CL), which can be any CL known in the art. In some aspects, a CL may be a kappa light chain. In some embodiments, a CL may be a lambda light chain. Antibody heavy and light chain constant regions are well known in the art, e.g., those provided in the IMGT database (www.imgt.org) or at www.vbase2.org/vbstat.php., both of which are incorporated by reference herein.

[0096] In some aspects, isolated anti-MYCT1 antibodies herein may be a full-length antibody or an antigen-binding fragment thereof. In some aspects, isolated antibodies herein may be a full-length antibody, which is an IgG molecule. In some aspects, isolated antibodies herein may be a Fab, a (Fab’)2, and/or a single-chain antibody. In some aspects, antibodies disclosed herein may be a single chain antibody (scFv). In some aspects, scFv antibody herein may comprise a VH fragment and a VL fragment, which may be linked via a linker. In accordance with these aspects, a linker incorporated between the two variable regions herein may be a flexible linker, a rigid linker, a cleavable linker, or any combination thereof. In some aspects, a linker incorporated between the two variable regions herein may be a flexible peptide linker, a rigid peptide linker, a cleavable peptide linker, or any combination thereof. In accordance with these aspects, a peptide linker incorporated between the two variable regions herein may be at least one amino acid. In some aspects, a peptide linker incorporated between the two variable regions herein may be about 1 amino acid to about 50 amino acids (e.g., about 1 , about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11 , about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21 , about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 32, about 34, about 36, about 38, about 40, about 42, about 44, about 46, about 48, about 50). In some aspects, a scFv antibody herein may comprise a VH fragment and a VL fragment, which may be linked via a flexible peptide linker.

[0097] In some aspects, a scFv antibody herein may be in the VH-VL orientation (from N-terminus to C-terminus). In some aspects, a scFv antibody herein may be in the VL-VH orientation (from N-terminus to C-terminus).

[0098] In some aspects, isolated antibodies herein may be a human antibody or a humanized antibody. Humanized antibodies refer to forms of non-human (e.g., murine) antibodies that are specific chimeric immunoglobulins, immunoglobulin chains, or antigen-binding fragments thereof that contain minimal sequence derived from non-human immunoglobulin. In some aspects, each of the exemplary antibodies described above may also contain a variant Fc region.

[0099] Polynucleotides, vectors and host cells can be used to prepare any one of the antibodies disclosed herein (e.g., an anti-MYCT1 antibody) using recombinant technology, as exemplified herein. In certain aspects, nucleic acids (i.e. , polynucleotides) encoding the heavy and light chain of an antibody as described herein can be cloned into one expression vector, each nucleotide sequence being in operable linkage to a suitable promoter. In some aspects, each of the polynucleotide sequences encoding the heavy chain and light chain may be in operable linkage to a distinct promoter. In some aspects, polynucleotide sequences encoding the heavy chain and the light chain may be in operable linkage with a single promoter, such that both heavy and light chains are expressed from the same promoter. In some embodiments, when necessary, an internal ribosomal entry site (IRES) can be inserted between the heavy chain and light chain encoding sequences.

[00100] In certain aspects, the polynucleotide sequences encoding the heavy chain and/or light chain of the antibodies described herein may share one or more polynucleotide sequences provided in Table 7.

[00101] In some aspects, isolated anti-MYCT1 antibodies may comprise a heavy chain variable region (VH) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 17, 53, 89 or 125. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 17. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 53. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 89. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 125.

[00102] In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the polynucleotide sequence of any one of SEQ ID NOs: 17, 53, 89 or 125. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the polynucleotide sequence of SEQ ID NO: 17. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the polynucleotide sequence of SEQ ID NO: 53. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the polynucleotide sequence of SEQ ID NO: 89. In some aspects, the anti-MYCT1 antibody comprises a VH that comprises the polynucleotide sequence of SEQ ID NO: 125.

[00103] In some aspects, isolated anti-MYCT1 antibodies may comprise a light chain variable region (VL) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 35, 71 , 107 or 143. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 35. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 71. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 107. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 143.

[00104] In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the polynucleotide sequence of any one of SEQ ID NOs: 35, 71 , 107 or 143. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the polynucleotide sequence of SEQ ID NO: 35. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the polynucleotide sequence of SEQ ID NO: 71. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the polynucleotide sequence of SEQ ID NO: 107. In some aspects, isolated anti-MYCT1 antibodies may comprise a VL that comprises the polynucleotide sequence of SEQ ID NO: 143.

[00105] In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 17, 53, 89 or 125; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 35, 71 , 107 or 143, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 17; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 35. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 53; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 71 . In some aspects, isolated anti-MYCT 1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 89; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 107. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the s polynucleotide equence of SEQ ID NO: 125; and a VL that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 143.

[00106] In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the polynucleotide sequence of any one of SEQ ID NOs: 17, 53, 89 or 125; and a VL that comprises the polynucleotide sequence of any one of SEQ ID NOs: 35, 71 , 107 or 143, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies may comprise a VH that comprises the polynucleotide sequence of SEQ ID NO: 17; and a VL that comprises the polynucleotide sequence of SEQ ID NO: 35. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the polynucleotide sequence of SEQ ID NO: 53; and a VL that comprises the polynucleotide sequence of SEQ ID NO: 71. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the polynucleotide sequence of SEQ ID NO: 89; and a VL that comprises the polynucleotide sequence of SEQ ID NO: 107. In some aspects, isolated anti-MYCT1 antibodies may comprise a VH that comprises the polynucleotide sequence of SEQ ID NO: 125; and a VL that comprises the polynucleotide sequence of SEQ ID NO: 143.

[00107] In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 9. In some aspects, isolated anti- MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 45. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 81 . In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 117.

[00108] In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NOs: 9. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NOs: 45. In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NOs: 81 . In some aspects, isolated anti-MYCT1 antibodies may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NOs: 117.

[00109] In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 27. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 63. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 99. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 135.

[00110] In some aspects, isolated anti-MYCT 1 antibodies may comprise a L1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 27. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 63. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 99. In some aspects, isolated anti-MYCT1 antibodies may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 135.

[00111] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99 or 135, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 9; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 27. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 45; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 63. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 81 ; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 99. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 117; and a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 135. [00112] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117; and a L1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 9; and a L1 that comprises the polynucleotide sequence of SEQ ID NO: 27. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 45; and a L1 that comprises the polynucleotide sequence of SEQ ID NO: 63. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 81 ; and a L1 that comprises the polynucleotide sequence of SEQ ID NO: 99. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 117; and a L1 that comprises the polynucleotide sequence of SEQ ID NO: 135.

[00113] In some aspects, isolated anti-MYCT 1 antibodies may comprise a heavy chain variable region 2 (H2) that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 11 . In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 47. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 83. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NOs: 119.

[00114] In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 11. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 47. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 83. In some aspects, isolated anti-MYCT1 antibodies may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 119.

[00115] In some aspects, isolated anti-MYCT 1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 29. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 65. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 101. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 137.

[00116] In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the polynucleotide sequence of SEQ ID NO: 29. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the polynucleotide sequence of SEQ ID NO: 65. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the polynucleotide sequence of SEQ ID NO: 101. In some aspects, isolated anti-MYCT1 antibodies may comprise a L2 that comprises the polynucleotide sequence of SEQ ID NO: 137. [00117] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 11 ; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 29. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 47; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 65. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 83; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 101. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 119; and a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 137.

[00118] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119; and a L2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 or 137, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 11 ; and a L2 that comprises the polynucleotide sequence of SEQ ID NO: 29. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 47; and a L2 that comprises the polynucleotide sequence of SEQ ID NO: 65. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 83; and a L2 that comprises the polynucleotide sequence of SEQ ID NO: 101. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H2 that comprises the polynucleotide sequence of SEQ ID NO: 119; and a L2 that comprises the polynucleotide sequence of SEQ ID NO: 137.

[00119] In some aspects, isolated anti-MYCT 1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 13. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 49. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 85. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NOs: 121 .

[00120] In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 . In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 13. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 49. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 85. In some aspects, isolated anti-MYCT1 antibodies may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 121 .

[00121] In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 31 . In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 67. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 103. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 139.

[00122] In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the polynucleotide sequence of SEQ ID NO: 31. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the polynucleotide sequence of SEQ ID NO: 67. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the polynucleotide sequence of SEQ ID NO: 103. In some aspects, isolated anti-MYCT1 antibodies may comprise a L3 that comprises the polynucleotide sequence of SEQ ID NO: 139.

[00123] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 ; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139, or any combination thereof. In some aspects, isolated anti- MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 13; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 31. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 49; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 67. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 85; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 103. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 121 ; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 139.

[00124] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 ; and a L3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 13; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 31. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 49; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 67. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 85; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 103. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H3 that comprises the polynucleotide sequence of SEQ ID NO: 121 ; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 139.

[00125] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 , or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 9; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 11 ; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 13, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 45; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 47; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 49, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 81 ; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 83; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 85, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 117; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 119; and a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 121 , or any combination thereof.

[00126] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117; a H2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119; and a H3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 , or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 9; a H2 that comprises the polynucleotide sequence of SEQ ID NO: 11 ; and a H3 that comprises the polynucleotide sequence of SEQ ID NO: 13, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 45; a H2 that comprises the sequence of SEQ ID NO: 47; and a H3 that comprises the polynucleotide sequence of SEQ ID NO: 49, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 81 ; a H2 that comprises the polynucleotide sequence of SEQ ID NO: 83; and a H3 that comprises the polynucleotide sequence of SEQ ID NO: 85, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 117; a H2 that comprises the polynucleotide sequence of SEQ ID NO: 119; and a H3 that comprises the polynucleotide sequence of SEQ ID NO: 121 , or any combination thereof.

[00127] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 27; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 29; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 31 , or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 63; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 65; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 67, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 99; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 101 ; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 103, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 135; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 137; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 139, or any combination thereof.

[00128] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135; a L2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137; and a L3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 27; a L2 that comprises the polynucleotide sequence of SEQ ID NO: 29; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 31 , or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 63; a L2 that comprises the polynucleotide sequence of SEQ ID NO: 65; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 67, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 99; a L2 that comprises the polynucleotide sequence of SEQ ID NO: 101 ; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 103, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a L1 that comprises the polynucleotide sequence of SEQ ID NO: 135; a L2 that comprises the polynucleotide sequence of SEQ ID NO: 137; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 139, or any combination thereof.

[00129] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 ; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 9; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 11 ; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NO: 13; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 27; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 29; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 31 , or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 45; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 47; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NO: 49; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 63; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 65; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 67, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 81 ; a H2 that comprises at least about 80% e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 83; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NO: 85; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the sequence of SEQ ID NO: 99; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 101 ; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 103, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 117; a H2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 119; a H3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of any one of SEQ ID NO: 121 ; a L1 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 135; a L2 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 137; and a L3 that comprises at least about 80% (e.g., about 85%, about 90%, about 95%, about 98%) identity to the polynucleotide sequence of SEQ ID NO: 139, or any combination thereof.

[00130] In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 9, 45, 81 , or 117; a H2 that comprises the sequence of any one of SEQ ID NOs: 11 , 47, 83, or 119; a H3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 13, 49, 85, or 121 ; a L1 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 27, 63, 99, or 135; a L2 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 29, 65, 101 , or 137; and a L3 that comprises the polynucleotide sequence of any one of SEQ ID NOs: 31 , 67, 103, or 139, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 9; a H2 that comprises the sequence of SEQ ID NO: 11 ; a H3 that comprises the polynucleotide sequence of any one of SEQ ID NO: 13; a L1 that comprises the polynucleotide sequence of SEQ ID NO: 27; a L2 that comprises the sequence of SEQ ID NO: 29; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 31 , or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 45; a H2 that comprises the polynucleotide sequence of SEQ ID NO: 47; a H3 that comprises the sequence of any one of SEQ ID NO: 49; a L1 that comprises the polynucleotide sequence of SEQ ID NO: 63; a L2 that comprises the sequence of SEQ ID NO: 65; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 67, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 81 ; a H2 that comprises the polynucleotide sequence of SEQ ID NO: 83; a H3 that comprises the polynucleotide sequence of any one of SEQ ID NO: 85; a L1 that comprises the polynucleotide sequence of SEQ ID NO: 99; a L2 that comprises the polynucleotide sequence of SEQ ID NO: 101 ; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 103, or any combination thereof. In some aspects, isolated anti-MYCT1 antibodies herein may comprise a H1 that comprises the polynucleotide sequence of SEQ ID NO: 117; a H2 that comprises the polynucleotide sequence of SEQ ID NO: 119; a H3 that comprises the polynucleotide sequence of any one of SEQ ID NO: 121 ; a L1 that comprises the polynucleotide sequence of SEQ ID NO: 135; a L2 that comprises the polynucleotide sequence of SEQ ID NO: 137; and a L3 that comprises the polynucleotide sequence of SEQ ID NO: 139, or any combination thereof. [00131] In certain aspects, the expression and/or production of the antibodies in the host cell can be promoted by expressing a leader peptide ahead of the variable region of the heavy or light chain of the antibody. In some embodiments, a leader peptide can be optimized for expression in a certain host cell (e.g., E. coli).

[00132] In some aspects, genetically engineered antibodies such as singlechain antibodies can be produced via, e.g., conventional recombinant technology or any methods known in the art. In some aspects, DNA encoding a monoclonal antibodies specific to a target antigen can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies). Once isolated, the DNA can be placed into one or more expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA can then be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. In some aspects, genetically engineered antibodies, such as chimeric or hybrid antibodies; can be prepared that have the binding specificity of a target antigen.

[00133] In some aspects, a single-chain antibody herein can be prepared via recombinant technology by linking a nucleotide sequence coding for a heavy chain variable region and a nucleotide sequence coding for a light chain variable region. In some aspects, a linker may be incorporated between the two variable regions. In some embodiments, techniques described for the_production of single chain antibodies can be adapted to produce a phage or yeast scFv library and scFv clones specific to the MYCT1 can be identified from the library following routine procedures. In some embodiments, positive clones can be subjected to further screening to identify those that bind to the specific epitopes on MYCT 1 . [00134] In some aspects, one or more vectors (e.g., expression vectors) having nucleic acids encoding any of the antibodies herein can be introduced into suitable host cells for producing the antibodies. In some aspects, host cells can be cultured under suitable conditions for expression of the antibody or any polypeptide chain thereof. In some aspects, antibodies or polypeptide chains thereof can be recovered by the cultured cells (e.g., from the cells or the culture supernatant) via a conventional method, e.g., affinity purification. In some aspects, polypeptide chains of the antibody herein can be incubated under suitable conditions for a suitable period of time allowing for production of the antibody.

[00135] In some aspects, methods for preparing an antibody described herein can include a recombinant expression vector that encodes both the heavy chain and the light chain of an antibody that binds to MYCT1 , as also described herein. In some aspects, a recombinant expression vector can be introduced into a suitable host cell (e.g., a dhfr-CHO cell) by a conventional method, e.g., calcium phosphate-mediated transfection. In some aspects, positive transformant host cells can be selected and cultured under suitable conditions allowing for the expression of the two polypeptide chains that form the antibody, which can be recovered from the cells or from the culture medium. In some aspects, the two chains recovered from the host cells can be incubated under suitable conditions allowing for the formation of the antibody.

[00136] In certain aspects, two recombinant expression vectors can be provided, one encoding the heavy chain of a disclosed antibody and the other encoding the light chain of the disclosed antibody. In some aspects, both of the two recombinant expression vectors can be introduced into a suitable host cell (e.g., dhfr-CHO cell) by a conventional method, e.g., calcium phosphate-mediated transfection. In some aspects, each of the expression vectors can be introduced into a suitable host cell. In some aspects, positive transformants can be selected and cultured under suitable conditions allowing for the expression of the polypeptide chains of the antibody. In some aspects, when the two expression vectors are introduced into the same host cells, the antibody produced therein can be recovered from the host cells or from the culture medium. In some aspects, the polypeptide chains can be recovered from the host cells or from the culture medium and then incubated under suitable conditions allowing for formation of the antibody. In some aspects, when the two expression vectors are introduced into different host cells, each of them can be recovered from the corresponding host cells or from the corresponding culture media. In some embodiments, two polypeptide chains can then be incubated under suitable conditions for formation of the antibody.

[00137] In certain aspects, standard molecular biology techniques can be used to prepare the recombinant expression vector, transfect the host cells, select for transformants, culture the host cells, and recover the antibodies from the culture medium. In some embodiments, some antibodies can be isolated by affinity chromatography with a Protein A or Protein G coupled matrix.

[00138] In additional aspects, antibodies herein can be characterized by identifying an epitope or more than one epitope to which the antigen binds, or “epitope mapping.” There are many methods known in the art for mapping and characterizing the location of epitopes on proteins, including, but not limited to, solving the crystal structure of an antibody-antigen complex, competition assays, gene fragment expression assays, and synthetic peptide-based assays. In some embodiments, epitope mapping can be used to determine the sequence, to which an antibody binds.

Chimeric antigen receptor

[00139] In some aspects, the present disclosure encompasses a chimeric antigen receptor (CAR) immune effector cell (CAR-immune effector cell) comprising an antigen binding domain which comprises antibody, or fragments thereof, that specifically binds to MYCT1 , disclosed herein. In one aspect, CAR-immune effector cell comprising an antigen binding domain comprising antibody, or fragments thereof that specifically binds to MYCT1 , comprises an amino acid or polynucleotide sequence listed in Table 7.

[00140] The hinge domain is a structure between the antigen recognition domain (e.g., antibody that binds MYCT1 ) and the cell plasma membrane; these sequences are generally derived from IgG subclasses (such as lgG1 and lgG4), IgD and CD8 domains, of which lgG1 has been the most extensively used for CAR construction. Currently, studies of the hinge domain mainly focus on the following four aspects: 1) reducing binding affinity to the Fey receptor, thereby eliminating off-target activation; 2) enhancing the single-chain variable fragment (scFv) flexibility, thereby relieving the spatial constraints between tumor antigens and CARs, and in turn promoting synapse formation between the CAR-immune effector cells and target cells;

3) reducing the distance between an scFv and the target epitope; and 4) facilitating the detection of CAR expression using anti-Fc reagents.

[00141] In one aspect, the hinge domain includes a hinge domain of a human protein selected from CD28, 4-1 BB (CD137), OX-40 (CD134), CD3 , T cell receptor a or [3 chain, CD45, CD4, CD5, CD8, CD8a, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, ICOS, CD154, functional derivatives and/or combinations thereof.

[00142] Typically, the extracellular domain, i.e. an antigen recognition domain (e.g., antibody that binds MYCT1 ) or target element is linked to the intracellular domain, i.e., the co-stimulatory and signaling domain(s) of the chimeric antigen receptor by a transmembrane domain. A transmembrane domain traverses the cell membrane, anchors the CAR to the immune effector cell surface, and connects the extracellular domain to the intracellular domain, thus impacting expression of the CAR on the immune effector cell surface.

[00143] The transmembrane domain includes a hydrophobic polypeptide that spans the cellular membrane. In particular, the transmembrane domain spans from one side of a cell membrane (extracellular) through to the other side of the cell membrane (intracellular or cytoplasmic).

[00144] The transmembrane domain may be in the form of an alpha helix or a beta barrel, or combinations thereof. The transmembrane domain may include a polytopic protein, which has many transmembrane segments, each alpha-helical, beta sheets, or combinations thereof.

[00145] In one aspect, the transmembrane domain that is naturally associated with one of the domains in the CAR is used. In another aspect, the transmembrane domain is selected or modified by amino acid substitution to avoid binding of such domains to the transmembrane domains of the same or different surface membrane proteins to minimize interactions with other members of the receptor complex. [00146] For example, the transmembrane domain is selected from a transmembrane domain of a T-cell receptor a or |3 chain, a CD3 chain, CD28, CD3s, CD45, CD4, CD5, CD7, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD68, OX-40 (CD134), 4-1 BB (CD137), ICOS, CD41 , CD154, functional derivatives and/or combinations thereof.

[00147] A chimeric antigen receptor of the present disclosure may comprise one or more costimulatory domain and/or one or more spacers. A costimulatory domain is derived from costimulatory proteins that enhance cytokine production, proliferation, cytotoxicity, and/or persistence in vivo.

[00148] In one aspect, the co-stimulatory domain is selected from OX-40 (CD134), CD27, CD28, CD30, CD40, PD-1 , CD2, CD7, CD258, Natural killer Group 2 member C (NKG2C), Natural killer Group 2 member D (NKG2D), B7-H3, a ligand that binds to at least one of CD83, ICAM-1 , LFA-1 (CD1 la/CD18), ICOS, and 4-1 BB (CD137), CDS, ICAM-1 , LFA-1 (CDIa/CD18), CD40, CD27, active fragments thereof, functional derivatives thereof, and combinations thereof.

[00149] A chimeric antigen receptor of the present disclosure also comprises a signaling domain that provides an intracellular signal to the immune effector cell upon antigen binding to the antigen recognition domain. The signaling domain of a chimeric antigen receptor of the present disclosure is responsible for activation of at least one of the effector functions of the immune effector cell in which the chimeric receptor is expressed. The term "effector function" refers to a specialized function of a differentiated cell. An effector function of an immune cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines. An effector function in a naive, memory, or memory-type immune cell may also include antigen-dependent proliferation. Thus, the term "intracellular domain" refers to the intracellular portion of a CAR that transduces the effector function signal upon binding of an antigen to the extracellular domain and directs the immune cell to perform a specialized function. Non-limiting examples of suitable signaling domains include the zeta chain of the immune-cell receptor or any of its homologs (e.g., eta, delta, gamma, or epsilon), MB-1 chain, 829, FcRIII, FcRI, and combinations of signaling molecules, such as CD3^ and CD28, CD27, 4-1 BB (CD137), DNAX-activating protein 10 (DAP10), OX-40 (CD134), and combinations thereof, as well as other similar molecules and fragments. Signaling domains of other activating proteins may be used, such as FcyRIII and Fc€RI. While usually the entire signaling domain will be employed, in many cases it will not be necessary to use the entire intracellular polypeptide. To that extent, a truncated portion of the signaling domain may be used as long as it still transduces the effector function signal. The term intracellular domain is also meant to include any truncated portion of the intracellular domain sufficient to transduce the effector function signal. Alternatively, or in addition, CAR-immune effector cells encompassed by the present disclosure may further comprise one or more suicide genes. As used herein, "suicide gene" refers to a nucleic acid sequence introduced to a CAR-immune effector cell by standard methods known in the art that, when activated, results in the death of the CAR-immune effector cell. Suicide genes may facilitate effective tracking and elimination of the CAR-immune effector cells in vivo if required. Facilitated killing by activating the suicide gene may occur by methods known in the art. Suitable suicide gene therapy systems known in the art include, but are not limited to, various the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene therapy systems or inducible caspase 9 protein. In an exemplary embodiment, a suicide gene is a CD34/thymidine kinase chimeric suicide gene.

[00150] Methods for CAR design, delivery and expression in immune cells, and the manufacturing of clinical-grade CAR-immune effector cell populations are known in the art. See, for example, Lee et al., Clin. Cancer Res., 2012, 18(10): 2780-90, hereby incorporated by reference in its entirety. For example, the engineered CARs may be introduced into immune effector cells using retroviruses, which efficiently and stably integrate a nucleic acid sequence encoding the chimeric antigen receptor into the target cell genome. An exemplary method for the viral vector production is described in the Methods to the Examples. Other methods known in the art include, but are not limited to, lentiviral transduction, transposon-based systems, direct RNA transfection, and CRISPR/Cas systems (e.g., type I, type II, or type III systems using a suitable Cas protein such Cas3, Cas4, Cas5, Cas5e (or CasD), Cas6, Cas6e, Cas6f, Cas7, Cas8a1 , Cas8a2, Cas8b, Cas8c, Cas9, Casi o, Casl Od, CasF, CasG, CasH, Csy1 , Csy2, Csy3, Cse1 (or CasA), Cse2 (or CasB), Cse3 (or CasE), Cse4 (or CasC), Csc1 , Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1 , Cmr3, Cmr4, Cmr5, Cmr6, Csb1 , Csb2, Csb3,Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csz1 , Csx15, Csf1 , Csf2, Csf3, Csf4, and Cu1966, etc.).

[00151] In some aspects, an immune effector cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.

[00152] In some aspects, the immune effector cells comprise any leukocyte involved in defending the body against infectious disease and foreign materials. For example, the immune effector cells can comprise lymphocytes, monocytes, macrophages, dendritic cells, mast cells, neutrophils, basophils, eosinophils, or any combinations thereof. In some aspects, the immune effector cells comprise T lymphocytes.

[00153] As disclosed herein, T cells can be T cell of any subset, non-limiting examples can include T helper cells (TH cells), Cytotoxic T cells (TC cells, or CTLs), Memory T cells, Regulatory T cells (Treg cells), or Natural killer T (NKT) cells.

[00154] T helper cells (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. These cells are also known as CD4+ T cells because they express the CD4 glycoprotein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. These cells can differentiate into one of several subtypes, including TH1 , TH2, TH3, TH17, TH9, or TFH, which secrete different cytokines to facilitate a different type of immune response.

[00155] Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen associated with MHC class I molecules, which are present on the surface of all nucleated cells. Through IL-10, adenosine and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state, which prevents autoimmune diseases.

[00156] Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with “memory” against past infections. Memory cells may be either CD4+ or CD8+. Memory T cells typically express the cell surface protein CD45RO.

[00157] Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ Treg cells have been described — naturally occurring Treg cells and adaptive Treg cells.

[00158] Natural killer T (NKT) cells, not to be confused with natural killer (NK) cells) bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigens presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by an MHC like I, CD1 d. In some aspects, NKT cells are invariant natural killer T (iNKT) cells. iNKT cells recognize CD1 d and are restricted by their T-cell Receptor (TCR) which in humans is Va24Ja18 and typically paired with V|311 . iNKT cells, further reduce graft-versus-host disease (GVHD).

[00159] In some aspects, the T cells comprise a mixture of CD4+ cells. In other aspects, the T cells are enriched for one or more subsets based on cell surface expression. For example, in some cases, the T comprise are cytotoxic CD8+ T lymphocytes. In some embodiments, the T cells comprise y5 T cells, which possess a distinct T-cell receptor (TCR) having one y chain and one 5 chain instead of a and [3 chains. [00160] Natural-killer (NK) cells are CD56+CD3- large granular lymphocytes that can kill virally infected and transformed cells, and constitute a critical cellular subset of the innate immune system. Unlike cytotoxic CD8+ T lymphocytes, NK cells launch cytotoxicity against tumor cells without the requirement for prior sensitization, and can also eradicate MHC-l-negative cells.

[00161] In some aspects, immune effector cells can be obtained from the subject to be treated (i.e. are autologous) and can be administered after genetic modification to express CAR with the disclosed anti-MYCT1 antigen recognition domain (e.g., anti-MYCT1 antibodies, or fragments thereof, disclosed herein), as adoptive transfer. In such aspects, adoptive transfer comprises procuring subject’s immune effector cells, followed by genetically modifying the cells to express the disclosed CARs with anti-MYCT1 antigen recognition domain, and infusing the modified cells back into the subject. In some aspects, immune effector cell lines or donor effector cells (allogeneic) are used. The immune effector cells for allogeneic therapy may be collected from a single subject or multiple subjects. Immune effector cells can be obtained from a number of sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and tumors. Immune effector cells can be obtained from blood collected from a subject using any number of techniques known to the skilled artisan, such as Ficoll™ separation. For example, cells from the circulating blood of an individual may be obtained by apheresis. In some aspects, immune effector cells can be isolated from peripheral blood lymphocytes by lysing the red blood cells and depleting the monocytes, for example, by centrifugation through a PERCOLL™ gradient or by counterflow centrifugal elutriation. A specific subpopulation of immune effector cells can be further isolated by positive or negative selection techniques. For example, immune effector cells can be isolated using a combination of antibodies directed to surface markers unique to the positively selected cells, e.g., by incubation with antibody- conjugated beads for a time period sufficient for positive selection of the desired immune effector cells. Alternatively, enrichment of immune effector cells population can be accomplished by negative selection using a combination of antibodies directed to surface markers unique to the negatively selected cells.

[00162] In some aspects, the expression of nucleic acids encoding CARs can be achieved by operably linking a nucleic acid encoding the CAR polypeptide comprising the disclosed anti-MYCT1 antigen recognition domain, to a promoter, and incorporating the construct into an expression vector. Typical cloning vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the desired nucleic acid sequence. In some aspects, immune effector cells are further comprises a modification of the endogenous T-cell Receptor Alpha Chain (TRAC) such that endogenous T cell receptor mediated signaling is blocked in the CAR-T cell.

[00163] In some aspects, the CAR comprising the disclosed anti-MYCT1 antigen recognition domain, can be cloned into a number of types of vectors. For example, the CAR comprising the disclosed anti-MYCT1 antigen recognition domain can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. In some aspects, non-limiting examples of vectors include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.

[00164] A number of viral based systems have been developed for gene transfer into mammalian cells. For example, the CAR comprising the disclosed anti- MYCT1 antigen recognition domain can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo.

Bispecific, multi-specific antibody, or hybrid antibody

[00165] In some aspects, the present disclosure further encompasses a bispecific antibody, a multi-specific antibody, or a hybrid antibody having at least two distinct binding domains with different specificities, with at least one domain comprising a H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed in Table 7. In some aspects, a bispecific antibody, a multi-specific antibody, or a hybrid antibody comprises an anti-MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and at least one of an immune cell engager (e.g., a T cell engager, an NK cell engager, an iNKT cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager). Such antibody constructs are recombinant protein constructs made from two flexibly linked antibody derived binding domains, with one binding domain specific for a selected tumor antigen on target tumor cells and the second binding domain that binds to and/or activates T cells, NK cells, iNKT cells, B cells, dendritic cells, or macrophage cells. In some aspects, the disclosed antibodies can transiently direct immune cells to the target tumor cells and/or activate the inherent cytolytic potential of immune cells against target tumor cells. In some aspects, a bispecific antibody, a multi-specific antibody, or a hybrid antibody comprises with at least one domain comprising an anti-MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second domain comprising a binding domain specific for an antigen expressed by B cell and/or plasma cell tumor cells. A bispecific antibody, a multispecific antibody, or a hybrid antibody construct can be produced by a variety of methods, including fusion of hybridomas, linking of Fab' fragments, or any other known method in the art.

[00166] In some aspects, the bispecific antibody, the multi-specific antibody, or the hybrid antibody comprises a T-cell engager (e.g., bispecific T cell engager (BiTE)) comprising first antigen recognition domain comprising an anti-MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment that bind to or activate T cells. In such aspects, a second antigen recognition domain comprising antibody or antigen-binding antibody fragment binds to one or more of CD2, CD3, CD4, CD5, CD6, CD8, CD25, CD27, CD28, CD30, CD40, CD40L, CD44, CD45, CD69, CD90, CRa, TCRp, TCRy, TCRC, ICOS, HVEM, LIGHT, 4-IBB, 0X40, DR3, GITR, TIMI, SLAM, or CD226

[00167] In some aspects, the bispecific antibody, the multi-specific antibody, or the hybrid antibody has a binding domain that engages NK cells. In such aspects, the bispecific antibody comprises a first antigen recognition domain comprising an anti- MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragments that bind to or activate NK cells. In such aspects, a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment binds to one or more of CD16 (e g., CD16a, CD16b, or both), NKp30, NKp40, NKp44, NKp46, NKG2D, DNAMI, DAP10, CRTAM, CD27, PSGL1 , CD96, CD100 (SEMA4D), NKp80, CD244 (also known as SLAMF4 or 2B4), SLAMF6, SLAMF7, KIR2DS2, KIR2DS4, KIR3DS 1 , KIR2DS3, KIR2DS5, KIR2DS 1 , CD94, NKG2C, NKG2E, or CD160.

[00168] In some aspects, the bispecific antibody, the multi-specific antibody, or the hybrid antibody has a binding domain that engages iNKT cells. In such aspects, the bispecific antibody comprises a first antigen recognition domain comprising an anti- MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragments that bind to or activate iNKT cells. In such aspects, a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment binds to CD3.

[00169] In some aspects, the bispecific antibody, the multi-specific antibody, or the hybrid antibody has a binding domain that engages B cells. In such aspects, the bispecific antibody comprises a first antigen recognition domain comprising an anti- MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragments that bind to or activate B cells. In such aspects, a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment binds to one or more of 0X40, CD40 or CD70.

[00170] In some aspects, the bispecific antibody, the multi-specific antibody, or the hybrid antibody has a binding domain that engages dendritic cells. In such aspects, the bispecific antibody comprises a first antigen recognition domain comprising an anti- MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragments that bind to or activate dendritic cells. In such aspects, a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment binds to one or more of CD2, 0X40, 4-IBB, TLR4, CD47, or STING.

[00171] In some aspects, the bispecific antibody, the multi-specific antibody, or the hybrid antibody has a binding domain that engages macrophage cell. In such aspects, the bispecific antibody comprises a first antigen recognition domain comprising an anti-MYCT1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragments that bind to or activate macrophage cells. In such aspects, a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment binds to one or more of 0X40, CD40, CD70, TLR4, TLR9, CD47 or STING agonist.

[00172] In some aspects, a bispecific antibody, a multi-specific antibody, or a hybrid antibody comprises a first antigen recognition domain comprising an anti-MYCT 1 H1 , H2, H3, L1 , L2, L3, VH and/or VL disclosed herein, and a second antigen recognition domain comprising an antibody or antigen-binding antibody fragments that bind to an antigen expressed by tumor cells. In some aspects, the antigen is an antigen expressed by sarcoma and/or breast cancer. In such aspects, a second antigen recognition domain comprising an antibody or antigen-binding antibody fragment binds to one or more of MAGE-A4, NY-ESO-1 , PRAME, TRAG-3/CSAGE, SSX, CTA, HLTF, ITGA10, PLCG1 , TTC3, HER2, MUC-1 , CEA, hTERT, STn, WT1 , and/or p53.

III. Compositions

[00173] In an aspect, the disclosure further encompasses a composition comprising anti-MYCT1 antibody, a fragment thereof, or a polynucleotide encoding the antibody. In some aspects, the composition of the disclosure comprises a composition that modulates MYCT1. Specifically, a composition that modulates MYCT1 may be a composition that down-regulates MYCT1 expression and/or activity. In certain aspects, the disclosed compositions comprise one or more of the antibodies, fragments thereof, or polynucleotide encoding the antibodies disclosed herein.

[00174] A composition of the invention may further comprise a pharmaceutically acceptable excipient, carrier or diluent. Further, a composition of the invention may contain preserving agents, solubilizing agents, stabilizing agents, wetting agents, emulsifiers, sweeteners, colorants, odorants, salts (substances of the present invention may themselves be provided in the form of a pharmaceutically acceptable salt), buffers, coating agents or antioxidants. [00175] In certain aspects, the compositions provided herein are pharmaceutical compositions comprising one or more of the antibodies, fragments thereof, or polynucleotide encoding the antibodies disclosed herein. In some aspects, pharmaceutical compositions herein may comprise one or more of the antibodies, fragments thereof, or polynucleotide encoding the antibodies disclosed herein and at least one pharmaceutically acceptable carrier and/or excipient. Pharmaceutically acceptable carriers or excipients suitable for the compositions described herein are well known to one of skill in the art of use for preserving and delivering antibodies or antibody fragments to any mammalian subject including humans and other mammals.

[00176] The compositions comprising anti-MYCT1 antibodies disclosed herein, or fragments thereof, may be formulated for administration, in any convenient manner, including by compositions for injection, transfusion, or implantation. The compositions described herein may be formulated for subcutaneous, intradermal, intratumoral, intranodal, intramedullar, intramuscular, intravenous (i.v.), or intraperitoneal, injection or administration. In some aspects, the disclosed compositions are formulated to be administered by intradermal or subcutaneous injection. In some aspects, the disclosed compositions are formulated to be administered by i.v. injection. The compositions may also be formulated, to be injected directly into a tumor, lymph node, or site of infection. In some aspects, the compositions disclosed herein are formulated for intravenous administration. In some aspects, the compositions disclosed herein are formulated for intraperitoneal injection.

[00177] In some aspects, the composition described herein can have liposomes containing the antibodies, fragments thereof, or the polynucleotides encoding the antibodies. In some aspects, liposomes for use herein can be generated by the reverse phase evaporation method with a lipid composition having phosphatidylcholine, cholesterol and PEG-derivatized phosphatidylethanolamine (PEG-PE). In some aspects, liposomes for use herein can be extruded through filters of defined pore size to yield liposomes with the desired diameter.

[00178] In some aspects, antibodies, fragments thereof, or the encoding polynucleotide(s) herein, can be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsions.

[00179] In some aspects, the compositions described herein can be formulated in sustained-release format. In some aspects, compositions herein to be used for in vivo administration may be sterile. In some aspects, this can be readily accomplished by, for example, filtration through sterile filtration membranes. In some aspects, therapeutic antibody compositions herein can be placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

[00180] In certain aspects, compositions described herein can be in unit dosage forms such as tablets, pills, capsules, powders, granules, solutions or suspensions, or suppositories, for oral, parenteral or rectal administration, or administration by inhalation or insufflation.

[00181] In some aspects, emulsion compositions herein can be those prepared by mixing an antibody with IntralipidTM or the components thereof (soybean oil, egg phospholipids, glycerol and water).

[00182] Suitable emulsions may be prepared using commercially available fat emulsions, such as IntralipidTM, LiposynTM, InfonutrolTM, LipofundinTM and LipiphysanTM. The active ingredient may be either dissolved in a pre-mixed emulsion composition or alternatively it may be dissolved in an oil (e.g., soybean oil, safflower oil, cottonseed oil, sesame oil, corn oil or almond oil) and an emulsion formed upon mixing with a phospholipid (e.g. egg phospholipids, soybean phospholipids or soybean lecithin) and water. It will be appreciated that other ingredients may be added, for example glycerol or glucose, to adjust the tonicity of the emulsion. Suitable emulsions will typically contain up to about 20% oil, for example, between about 5% and about 20%. The fat emulsion can comprise fat droplets between about 0.1 pm and about 1.0 pm, particularly about 0.1 pm and 0.5 pm, and have a pH in the range of about 5.5 to about 8.0.

[00183] In some aspects, pharmaceutical compositions herein for inhalation or intranasal administration may include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. In some aspects, liquid or solid compositions herein can contain suitable pharmaceutically acceptable excipients as set out above. In other aspects, the compositions can be administered by the oral or nasal respiratory route for local or systemic effect.

[00184] In some aspects, compositions can be in sterile pharmaceutically acceptable solvents can be nebulized by use of gases. In some aspects, nebulized solutions herein can be breathed directly from the nebulizing device or the nebulizing device can be attached to a face mask, tent or intermittent positive pressure breathing machine. In some embodiments, solution, suspension or powder compositions herein can be administered, preferably orally or nasally, from devices which deliver the formulation in an appropriate manner.

Components of the composition

[00185] In certain aspects, the composition disclosed herein may be a pharmaceutical composition. In such aspects, the composition comprises an anti- MYCT1 antibody as described above, as an active ingredient, and at least one pharmaceutically acceptable excipient.

[00186] The pharmaceutically acceptable excipient may be a diluent, a binder, a filler, a buffering agent, a pH modifying agent, a disintegrant, a dispersant, a preservative, a lubricant, taste-masking agent, a flavoring agent, or a coloring agent. The amount and types of excipients utilized to form pharmaceutical compositions may be selected according to known principles of pharmaceutical science.

(i) Diluent

[00187] In one aspect, the excipient may be a diluent. The diluent may be compressible (i.e. , plastically deformable) or abrasively brittle. Non-limiting examples of suitable compressible diluents include microcrystalline cellulose (MCC), cellulose derivatives, cellulose powder, cellulose esters (i.e., acetate and butyrate mixed esters), ethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcell-lose, sodium carboxymethylcellulose, corn starch, phosphated corn starch, pregelatinized corn starch, rice starch, potato starch, tapioca starch, starch-lactose, starch-calcium carbonate, sodium starch glycolate, glucose, fructose, lactose, lactose mono-hydrate, sucrose, xylose, lactitol, mannitol, malitol, sorbitol, xylitol, maltodextrin, and trehalose. Non-limiting examples of suitable abrasively brittle diluents include dibasic calcium phosphate (anhydrous or dihydrate), calcium phosphate tribasic, calcium carbonate, and magnesium carbonate.

(ii) Binder

[00188] In another aspect, the excipient may be a binder. Suitable binders include, but are not limited to, starches, pregelatinized starches, gelatin, polyvinylpyrrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, polypeptides, oligopeptides, and combinations thereof.

(iii) Filler

[00189] In another aspect, the excipient may be a filler. Suitable fillers include, but are not limited to, carbohydrates, inorganic compounds, and polyvinylpyrrolidone. By way of non-limiting example, the filler may be calcium sulfate, both di- and tri-basic, starch, calcium carbonate, magnesium carbonate, microcrystalline cellulose, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starches, lactose, sucrose, mannitol, or sorbitol.

(iv) Buffering Agent

[00190] In still another aspect, the excipient may be a buffering agent. Representative examples of suitable buffering agents include, but are not limited to, phosphates, carbonates, citrates, tris buffers, and buffered saline salts (e.g., Tris buffered saline or phosphate buffered saline).

(v) pH Modifier [00191] In various aspects, the excipient may be a pH modifier. By way of non-limiting example, the pH modifying agent may be sodium carbonate, sodium bicarbonate, sodium citrate, citric acid, or phosphoric acid.

(vi) Disintegrant

[00192] In a further aspects, the excipient may be a disintegrant. The disintegrant may be non-effervescent or effervescent. Suitable examples of non- effervescent disintegrants include, but are not limited to, starches such as com starch, potato starch, pre-gelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pecitin, and tragacanth. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid and sodium bicarbonate in combination with tartaric acid.

(vii) Dispersant

[00193] In yet another aspect, the excipient may be a dispersant or dispersing enhancing agent. Suitable dispersants may include, but are not limited to, starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose.

(viii) Excipient

[00194] In another alternate aspect, the excipient may be a preservative. Non-limiting examples of suitable preservatives include antioxidants, such as BHA, BHT, vitamin A, vitamin C, vitamin E, or retinyl palmitate, citric acid, sodium citrate; chelators such as EDTA or EGTA; and antimicrobials, such as parabens, chlorobutanol, or phenol.

(ix) Lubricant

[00195] In a further aspect, the excipient may be a lubricant. Non-limiting examples of suitable lubricants include minerals such as talc or silica; and fats such as vegetable stearin, magnesium stearate, or stearic acid.

(x) Taste-Masking Agent

[00196] In yet another aspect, the excipient may be a taste-masking agent. Taste-masking materials include cellulose ethers; polyethylene glycols; polyvinyl alcohol; polyvinyl alcohol and polyethylene glycol copolymers; monoglycerides or triglycerides; acrylic polymers; mixtures of acrylic polymers with cellulose ethers; cellulose acetate phthalate; and combinations thereof.

(xi) Flavoring Agent

[00197] In an alternate aspect, the excipient may be a flavoring agent. Flavoring agents may be chosen from synthetic flavor oils and flavoring aromatics and/or natural oils, extracts from plants, leaves, flowers, fruits, and combinations thereof.

(xii) Coloring Agent

[00198] In still a further aspect, the excipient may be a coloring agent. Suitable color additives include, but are not limited to, food, drug and cosmetic colors (FD&C), drug and cosmetic colors (D&C), or external drug and cosmetic colors (Ext. D&C).

[00199] The weight fraction of the excipient or combination of excipients in the composition may be about 99% or less, about 97% or less, about 95% or less, about 90% or less, about 85% or less, about 80% or less, about 75% or less, about 70% or less, about 65% or less, about 60% or less, about 55% or less, about 50% or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 25% or less, about 20% or less, about 15% or less, about 10% or less, about 5% or less, about 2%, or about 1 % or less of the total weight of the composition.

[00200] The present disclosure encompasses pharmaceutical compositions comprising an anti-MYCT1 antibody, fragment thereof, or a polynucleotide encoding the antibody described herein, so as to facilitate administration and promote stability of the active agent. For example, an anti-MYCT1 antibody, fragment thereof, or a polynucleotide encoding the antibody of this disclosure may be admixed with at least one pharmaceutically acceptable carrier or excipient resulting in a pharmaceutical composition which is capably and effectively administered (given) to a living subject, such as to a suitable subject (i.e. “a subject in need of treatment” or “a subject in need thereof”). Methods of preparing and administering anti-MYCT1 antibodies, fragments thereof, or a polynucleotides encoding the antibodies disclosed herein to a subject in need thereof are well known to or are readily determined by those skilled in the art. The route of administration of an anti-MYCT1 antibody, fragment thereof, or a polynucleotide encoding the antibody can be, for example, peripheral, oral, parenteral, by inhalation or topical.

[00201] Pharmaceutical compositions for effective administration are deliberately designed to be appropriate for the selected mode of administration, and pharmaceutically acceptable excipients such as compatible carriers, dispersing agents, buffers, surfactants, preservatives, solubilizing agents, isotonicity agents, stabilizing agents and the like are used as appropriate.

[00202] Non-limiting examples of pharmaceutically acceptable carriers, include physiological saline, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene- polyoxypropylene-block polymers, polyethylene glycol, wool fat or a combination thereof.

[00203] Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal and the like. In many cases, isotonic agents can be included, for example, sugars, polyalcohols, such as mannitol, sorbitol, or sodium chloride in the composition.

[00204] Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[00205] Compositions disclosed herein can be frozen or lyophilized for storage and reconstituted in a suitable sterile carrier prior to use.

Ill [00206] In some aspects, anti-MYCT1 antibodies may be formulated for parenteral administration. Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of nonaqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives can also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like. Parenteral formulations can be a single bolus dose, an infusion or a loading bolus dose followed with a maintenance dose. These compositions can be administered at specific fixed or variable intervals, e.g., once a day, or on an “as needed” basis.

[00207] Certain pharmaceutical compositions, as disclosed herein, can be orally administered in an acceptable dosage form including, e.g., capsules, tablets, aqueous suspensions or solutions. Certain pharmaceutical compositions also can be administered by nasal aerosol or inhalation. Such compositions can be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, and/or other conventional solubilizing or dispersing agents.

[00208] The amount of an anti-MYCT 1 antibody to be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. The composition can be administered as a single dose, multiple doses or over an established period of time in an infusion. Dosage regimens also can be adjusted to provide the optimum desired response (e.g., a therapeutic or prophylactic response).

[00209] In some aspects, concentrations of antibodies disclosed herein can be a pre-determined concentration or a standard concentration. In some aspects, the antibodies disclosed herein can be in a concentration of about 1 micrograms/milliliters (mg/ml) to about 500 mg/ml, about 1 mg/ml to about 250 mg/ml, about 1 mg/ml to about 200 mg/ml, about 1 mg/ml to about 150 mg/ml, about 1 mg/ml to about 100 mg/ml, about 1 mg/ml to about 75 mg/ml, about 1 mg/ml to about 50 mg/ml, about 0.1 mg/ml to about 100 mg/ml, or other suitable concentration. In some embodiments, the antibody is formulated to a concentration of about 30 mg/ml. In some embodiments, the antibody is lyophilized. In some aspects, the antibody is diluted in a suitable solution to a suitable concentration prior to administration (e.g., in a therapeutic application described below).

[00210] In some aspects, compositions described herein can further comprise active agents in addition to the antibodies, fragments thereof or polynucleotides provided herein. Non limiting examples of additional active agents include but are not restricted to antibiotics, anti-pyrectics, antimicrobials, antifungals, NSAIDs, chemotherapeutic and anticancer agents.

[00211] In further aspects, the composition comprising disclosed anti- MYCT1 antibody, fragment thereof, or polynucleotides encoding the antibodies may be administered to a subject in need thereof. In some aspects, the disclosed compositions comprise may be administered to a subject in need thereof wherein the subject is a human subject. In some aspects, the disclosed compositions comprise may be administered to a subject in need thereof wherein the subject is a subject having, suspected of having, or at risk for an angiogenesis associated disease. In some aspects, an angiogenesis associated disease is age-related macular degeneration, ischemic retinopathy, intraocular neovascularization, corneal neovascularization, retinal neovascularization, choroidal neovascularization, diabetic macular edema, diabetic retina ischemia, diabetic retinal edema, diabetic retinopathy, cancers, rheumatoid arthritis, endometriosis, or alopecia.

[00212] In some aspects, the disclosed compositions may be administered to a subject in need thereof, wherein the subject is having, suspected of having, or at risk for a cancer. In some aspects, the cancer is a cancer comprising cancer cells with increased endogenous MYCT1 expression or activity. Such cancer cells express MYCT1 at high higher levels than normal cells (e.g., control breast cells) or cancer cells, when compared to cancer cells across patient samples. Such cells express MYCT1 at levels higher than average levels expressed by a population of cancer cells (e.g., average levels of MYCT1 expression in breast cancer cells). In some aspects, the cancer cells express MYCT1 at levels at least 10% higher, for e.g., 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or more, higher than normal cells (e.g., control breast cells) or higher than cancer cells, when compared to cancer cells across patient samples.

[00213] In some aspects the cancer is a sarcoma. In some aspects, the cancer is Ewing’s sarcoma, Soft-tissue sarcoma, liposarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma, Kaposi sarcoma, osteosarcoma, fibrosarcoma, dermatofibrosarcoma, aggressive fibromatosis, rhabdomyosarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, chondrosarcoma, gastrointestinal stroma tumor, or a uterine sarcoma. In some aspects, the cancer is breast cancer. In some aspects, cancer is ductal carcinoma in situ, invasive ductal carcinoma, inflammatory breast cancer, or a metastatic breast cancer.

[00214] In some aspects, the composition comprising disclosed anti- MYCT1 antibody, fragment thereof, or polynucleotides encoding the antibodies, can decreases and/or inhibits activity, function, expression and/or accumulation of MYCT1. In some aspects, the administration of the composition comprising disclosed anti- MYCT1 antibody, fragment thereof, or polynucleotides encoding the antibodies, results in reduction of activity, function, expression and/or accumulation of MYCT1 in the subject. In some aspects, the administration of the composition comprising antibody, fragment thereof, or polynucleotides encoding the anti-MYCT1 antibodies described herein results in reduction of activity, function, expression and/or accumulation of MYCT1 by at least about 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to activity, function, expression and/or accumulation of MYCT1 before administration of the antibody, fragment thereof, or polynucleotides encoding the antibodies (baseline) or a control subject not receiving the treatment.

[00215] In some aspects, the composition comprising anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies reduces the tumor volume in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor volume before administration of the anti- MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment.

[00216] In some aspects, the composition comprising anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies reduce the tumor volume in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor volume before administration of the anti- MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment. Tumor volume in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as X ray, CT scan, bone marrow biopsy, serum protein electrophoresis (SPEP), or MRI.

[00217] In some aspects, the composition comprising anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies reduce the tumor angiogenesis in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor angiogenesis before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment. Tumor angiogenesis in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as counting the number of blood vessels in a given area using a stereomicroscope, or by measuring expression of biomarkers associated with angiogenesis including a _v [33 Integrin, endoglin, and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2.

[00218] In some aspects, the composition comprising anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, may increase the immune response against cancer cells or anti-tumor immunity in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to immune response or anti-tumor immunity before administration of the antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment. Immune response against cancer cells can be measured using biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, and density of tumor infiltrating lymphocyte (TIL).

[00219] In further aspects, a composition of the disclosure may optionally comprise one or more immune checkpoint inhibitor compounds. Inhibitors may target any immune checkpoint known in the art, including but not limited to, CTLA-4, PDL1 , PDL2, PD1 , B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, CSF-1 R, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK1 , CHK2, A2aR, CD28, CD86, CD69, CD48, CD113, CEACAM-1 , Galectin-1 , TIGIT, GPR56, CD48, GARP, PD1 H, LAIR1 , TIM1 , TIM4 and the B-7 family of ligands. In some aspects, the immune checkpoint inhibitors comprise CTLA-4 blocking antibodies (Ipilimumab (Yervoy), Tremelimumab (Imjuno)), PD-1 inhibitors (Pembrolizumab (Keytruda), Nivolumab (Opdivo), Cemiplimab (Libtayo), CT- 011 (Pidilizumab), AMP224), PD-L1 inhibitors (Atezolizumab (tecentriq), Avelumab (Bavencio), Durvalumab (Imfinzi), BMS- 936559), Lag3 inhibitors (Relatlimab), combination of Lag3 and PD1 inhibitor (PD-1 inhibitor nivolumab (Opdualag) 0X40 inhibitor (MEDI6469), CD160 inhibitor (BY55). Non-limiting examples of inhibitors of CSF-1 R include PLX3397, PLX486, RG7155, AMG820, ARRY-382, FPA008, IMC-CS4, JNJ-40346527, MCS 110, or any combination thereof.

[00220] In certain aspects, a composition of the disclosure may comprise one or more PD-1 inhibitor and/or PD-L1 inhibitor compounds. Non limiting examples of immune checkpoint compounds include monoclonal antibodies that target either PD-1 or PD-L1. In some aspects, monoclonal antibodies that target PD-1 or PD-L1 comprise Pembrolizumab, Nivolumab, Cemiplimab, Atezolizumab, Avelumab, Durvalumab, and/or Ipilimumab.

[00221] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may be administered to a subject having a cancer that is initially sensitive to immune checkpoint inhibitor treatment and later becomes insensitive to immune checkpoint inhibitor treatment. In some aspects, the combination of anti- MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may be administered to a subject having a cancer that is insensitive to immune checkpoint inhibitor treatment. In some aspects, the disclosed anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies sensitizes a cancer to immune checkpoint inhibitors.

[00222] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may reduce the tumor volume in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to tumor volume before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with immune checkpoint inhibitor compound (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving immune checkpoint inhibitor compound alone. In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound reduces the tumor volume in a subject by at least 25%. Tumor volume in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as X ray, CT scan, bone marrow biopsy, serum protein electrophoresis (SPEP), or MRI.

[00223] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies with an immune checkpoint inhibitor compound reduce the tumor angiogenesis in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor angiogenesis before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving immune checkpoint inhibitor compound alone. Tumor angiogenesis in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as counting the number of blood vessels in a given area using a stereomicroscope, or by measuring expression of biomarkers associated with angiogenesis including a _v [33 Integrin, endoglin, and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2.

[00224] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may increase the immune response or anti-tumor immunity against cancer cells in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to immune response or anti-tumor immunity before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with immune checkpoint inhibitor compound (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving immune checkpoint inhibitor compound alone. Immune response against cancer cells can be measured using biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, and density of tumor infiltrating lymphocyte (TIL).

[00225] Still further, a composition of the disclosure may optionally comprise one or more VEGF inhibitors. In non-limiting examples, a composition of the disclosure may optionally comprise one or more of axitinib, bevacizumab, cabozantinib, lapatinib, Lenvatinib, pazopanib, ponatinib, ramucirumab, ranibizumab, regorafenib, sorafenib, sunitinib and/or vandetanib.

[00226] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with a VEGF inhibitor may reduce the tumor volume in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to tumor volume before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with VEGF inhibitor (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving VEGF inhibitor alone. In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an VEGF inhibitor compound reduces the tumor volume in a subject by at least 25%. Tumor volume in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as X ray, CT scan, bone marrow biopsy, serum protein electrophoresis (SPEP), or MRI.

[00227] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies with a VEGF inhibitor reduce the tumor angiogenesis in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor angiogenesis before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving a VEGF inhibitor alone. Tumor angiogenesis in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as counting the number of blood vessels in a given area using a stereomicroscope, or by measuring expression of biomarkers associated with angiogenesis including a _v p3 Integrin, endoglin, and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2.

[00228] In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with a VEGF inhibitor compound may increase the immune response or anti-tumor immunity against cancer cells in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to immune response or anti-tumor immunity before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with a VEGF inhibitor (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving a VEGF inhibitor alone. Immune response against cancer cells can be measured using biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, and density of tumor infiltrating lymphocyte (TIL).

[00229] As noted above, the agents or compositions described herein can also be used in combination with other therapeutic agents, as described further below. Thus, in addition to the therapies described herein, one may also provide to the subject other therapies known to be efficacious for treatment of the disease, disorder, or condition. In various examples, a method further comprises administering to the patient an additional cancer treatment. In some examples, the additional cancer treatment is chosen from the group comprising surgery, radiotherapy, chemotherapy, toxin therapy, immunotherapy, cryotherapy, gene therapy, and combinations thereof. Examples of anti-angiogenic therapeutic targets useful in accordance with the disclosure include EGF, VEGF, FGF, and matrix remodeling proteins. In various examples, a chemotherapy agent is a drug or drug formulation. Non-limiting examples of drug formulations include polymeric micelle formulations, liposomal formulations, dendrimer formulations, polymer-based nanoparticle formulations, silica-based nanoparticle formulations, nanoscale coordination polymer formulations, nanoscale metal-organic framework formulations, inorganic nanoparticle formulations, and the like.

[00230] Various chemotherapy agents (e.g., chemotherapy drugs) can be used. Any FDA approved chemotherapy agent (e.g., chemotherapy drugs) can be used. Combinations of chemotherapy agents may be used. Chemotherapeutic and anticancer agents commonly used to treat cancer, and which may be used in combination with any of the compositions disclosed herein include but are not limited to platinum compounds (such as cisplatin or carboplatin), and taxane compounds such as paclitaxel (Taxol®) or docetaxel (Taxotere®). Other chemotherapeutic agents used to treat cancer and which may be used in combination with any of the compositions disclosed herein, include but are not limited to: Albumin bound paclitaxel (nab-paclitaxel, Abraxane®), Pemetrexed (Alimta®), Irinotecan (CPT-11 , Camptosar®), Cyclophosphamide (Cytoxan®), Liposomal doxorubicin (Doxil®), Gemcitabine (Gemzar®), Altretamine (Hexalen®), Ifosfamide (Ifex®), Melphalan (Alkeran), Vinorelbine (Navelbine®), Topotecan (Hycamtin), Etoposide (VP-16), and Capecitabine (Xeloda®). [00231] In some aspects, the additional drug or therapeutically active agent may be a genotoxic agent (e.g., a DNA-damaging agent or drug). As used herein “genotoxic therapy” refers to a treat of a tumor or cancer which utilizes the destructive properties of the treatment to induce DNA damage into tumor or cancer cells. The treatment is traditionally part of standardized regime. Any damage done to a tumor cancer is passed on to descendent cancer cells as proliferation continues. If this damage is severe enough, it will induce cells to undergo apoptosis. In non-limiting examples, a genotoxic therapy may include y-irradiation , alkylating agents such as nitrogen mustards (chlorambucil, cyclophosphamide, ifosfamide, melphalan), nitrosoureas (streptozocin, carmustine, lomustine), alkyl sulfonates (busulfan), triazines (dacarbazine, temozolomide) and ethylenimines (thiotepa, altretamine), platinum drugs such as cisplatin, carboplatin, oxalaplatin, antimetabolites such as 5-fluorouracil, 6- mercaptopurine, capecitabine, cladribine. clofarabine, cytarabine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, pemetrexed, pentostatin, thioguanine, anthracyclines such as daunorubicin, doxorubicin, epirubicin, idarubicin , anti-tumor antibiotics such as actinomycin-D, bleomycin, mitomycin-C, mitoxantrone, topoisomerase inhibitors such as topoisomerase I inhibitors (topotecan, irinotecan) and topoisomerase II inhibitors (etoposide, teniposide, mitoxantrone), mitotic inhibitors such as taxanes (paclitaxel, docetaxel), epothilones (ixabepilone), vinca alkaloids (vinblastine, vincristine, vinorelbine), and estramustine.

[00232] Treatment in accord with the methods described herein can be performed prior to, concurrent with, or after conventional treatment modalities for a cancer or tumor.

[00233] Dosages of an additional drug or therapeutically active agent can vary between wide limits, depending upon the disease or disorder to be treated, the age and condition of the subject to be treated. In an aspect where the composition further comprising at least one additional drug or therapeutically active agent is contacted with a sample, the concentration of the at least one additional drug or therapeutically active agent may be from about 0.01 pM to about 10 pM. Alternatively, the concentration of the at least one additional drug or therapeutically active agent may be from about 0.01 pM to about 5 pM. For example, the concentration of the at least one additional drug or therapeutically active agent may be about 0.01 , about 0.05, about 0.1 , about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1 , about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10 pM. Additionally, the concentration of the at least one additional drug or therapeutically active agent be greater than 10 pM. For example, the concentration of the at least one additional agent may be 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 about 100 pM.

[00234] In an aspect where the composition further comprising at least one additional drug or therapeutically active agent administered to a subject, the dose of the additional drug or therapeutically active agent may be from about 0.1 mg/kg to about 500 mg/kg. For example, the dose of the least one additional drug or therapeutically active agent may be about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg/kg, about 15 mg/kg, about 20 mg/kg, or about 25 mg/kg. Alternatively, the dose of the least one additional drug or therapeutically active agent may be about 25 mg/kg, about 50 mg/kg, about 75 mg/kg, about 100 mg/kg, about 125 mg/kg, about 150 mg/kg, about 175 mg/kg, about 200 mg/kg, about 225 mg/kg, or about 250 mg/kg. Additionally, the dose of the least one additional drug or therapeutically active agent may be about 300 mg/kg, about 325 mg/kg, about 350 mg/kg, about 375 mg/kg, about 400 mg/kg, about 425 mg/kg, about 450 mg/kg, about 475 mg/kg, or about 500 mg/kg.

[00235] Generally, a safe and effective amount of a composition is administered, for example, that amount that would cause the desired therapeutic effect in a subject while minimizing undesired side effects. In various aspects, an effective amount of a composition described herein can substantially reduce the growth or spread of cancer in a subject. In some aspects, an effective amount is an amount capable of treating a cancer or tumor. In some aspects, an effective amount is an amount capable of treating one or more symptoms associated with a cancer or tumor.

[00236] The amount of a composition described herein that can be combined with a pharmaceutically acceptable carrier to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. It will be appreciated by those skilled in the art that the unit content of agent contained in an individual dose of each dosage form need not in itself constitute a therapeutically effective amount, as the necessary therapeutically effective amount could be reached by administration of a number of individual doses.

[00237] Toxicity and therapeutic efficacy of compositions described herein can be determined by standard pharmaceutical procedures in cell cultures or experimental animals for determining the LD50 (the dose lethal to 50% of the population) and the ED50, (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index that can be expressed as the ratio LD50/ED50, where larger therapeutic indices are generally understood in the art to be optimal.

[00238] The specific therapeutically effective dose level for any particular subject will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the subject; the time of administration; the route of administration; the rate of excretion of the composition employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts (see e.g., Koda-Kimble et al. (2004) Applied Therapeutics: The Clinical Use of Drugs, Lippincott Williams & Wilkins, ISBN 0781748453; Winter (2003) Basic Clinical Pharmacokinetics, 4th ed., Lippincott Williams & Wilkins, ISBN 0781741475; Sharqel (2004) Ap-plied Biopharmaceutics & Pharmacokinetics, McGraw-Hill/Appleton & Lange, ISBN 0071375503). For example, it is well within the skill of the art to start doses of the composition at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose may be divided into multiple doses for purposes of administration. Consequently, single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. It will be understood, however, that the total daily usage of the compounds and compositions of the present disclosure will be decided by an attending physician within the scope of sound medical judgment.

[00239] Administration of a composition as disclosed herein can occur as a single event or over a time course of treatment. For example, a composition can be administered daily, weekly, bi-weekly, or monthly. For treatment of acute conditions, the time course of treatment will usually be at least several days. Certain conditions could extend treatment from several days to several weeks. For example, treatment could extend over one week, two weeks, or three weeks. For more chronic conditions, treatment could extend from several weeks to several months or even a year or more.

[00240] Where there is more than one administration in the present methods, the administrations can be spaced by time intervals of one minute, two minutes, three, four, five, six, seven, eight, nine, ten, or more minutes, by intervals of about one hour, two hours, three, four, five, six, seven, eight, nine, ten, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24 hours, and so on. In the context of hours, the term "about" means plus or minus any time interval within 30 minutes. The administrations can also be spaced by time intervals of one day, two days, three days, four days, five days, six days, seven days, eight days, nine days, ten days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, and combinations thereof. The disclosure is not limited to dosing intervals that are spaced equally in time, but encompass doses at non-equal intervals, such as a priming schedule consisting of administration at 1 day, 4 days, 7 days, and 25 days, just to provide a non-limiting example.

[00241] A dosing schedule of, for example, once/week, twice/week, three times/week, four times/week, five times/week, six times/week, seven times/week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, and the like, is available for the disclosure. The dosing schedules encompass dosing for a total period of time, for example, one week, two weeks, three weeks, four weeks, five weeks, six weeks, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, and twelve months. [00242] Provided are cycles of the above dosing schedules. The cycle can be repeated about, e.g., every seven days; every 14 days; every 21 days; every 28 days; every 35 days; 42 days; every 49 days; every 56 days; every 63 days; every 70 days; and the like. An interval of non-dosing can occur between a cycle, where the interval can be about, e.g., seven days; 14 days; 21 days; 28 days; 35 days; 42 days; 49 days; 56 days; 63 days; 70 days; and the like. In this context, the term "about" means plus or minus one day, plus or minus two days, plus or minus three days, plus or minus four days, plus or minus five days, plus or minus six days, or plus or minus seven days.

IV. Methods

[00243] The present disclosure further provides a method of treating a subject with cancer. In some aspects, methods described herein may comprise administering to a subject in need thereof an effective amount of one or more of the anti-MYCT1 antibodies disclosed herein, or fragments thereof or one or more of the pharmaceutical compositions disclosed herein. In some aspects, methods herein may comprise administering to a subject in need thereof wherein the subject is a human subject. In some aspects, methods herein may comprise administering to a subject in need thereof wherein the subject is a subject having, suspected of having, or at risk for an angiogenesis associated disease. In some aspects, an angiogenesis associated disease is age-related macular degeneration, ischemic retinopathy, intraocular neovascularization, corneal neovascularization, retinal neovascularization, choroidal neovascularization, diabetic macular edema, diabetic retina ischemia, diabetic retinal edema, diabetic retinopathy, cancers, rheumatoid arthritis, endometriosis, or alopecia.

[00244] In some aspects, methods herein may comprise administering to a subject having, suspected of having, or at risk for a cancer. In some aspects, the cancer is a cancer comprising cancer cells with increased endogenous MYCT1 expression. Such cancer cells express MYCT1 at high higher levels than normal cells (e.g., control breast cells) or cancer cells, when compared to cancer cells across patient samples. Such cells express MYCT1 at levels higher than average levels expressed by a population of cancer cells (e.g., average levels of MYCT1 expression in breast cancer cells). In some aspects, the cancer cells express MYCT1 at levels at least 10% higher, for e.g., 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or more, higher than normal cells (e.g., control breast cells) or higher than cancer cells, when compared to cancer cells across patient samples. In such aspects, the method comprises administering to the subject, a therapeutically effective amount of plurality of one or more of the anti-MYCT 1 antibodies disclosed herein, or fragments thereof or one or more of the pharmaceutical compositions disclosed herein.

[00245] In some aspects of the method, the cancer is a sarcoma. In some aspects, the cancer is Ewing’s sarcoma, Soft-tissue sarcoma, liposarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma, Kaposi sarcoma, osteosarcoma, fibrosarcoma, dermatofibrosarcoma, aggressive fibromatosis, rhabdomyosarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, chondrosarcoma, gastrointestinal stroma tumor, or a uterine sarcoma. In some aspects, the cancer is breast cancer. In some aspects, cancer is ductal carcinoma in situ, invasive ductal carcinoma, inflammatory breast cancer, or a metastatic breast cancer.

[00246] In some aspects, the administration of the disclosed anti-MYCT 1 antibody, fragment thereof, or polynucleotides encoding the antibodies, can decreases and/or inhibits activity, function, expression and/or accumulation of MYCT1. In some aspects, the administration of the composition comprising disclosed anti-MYCT1 antibody, fragment thereof, or polynucleotides encoding the antibodies, results in reduction of activity, function, expression and/or accumulation of MYCT1 in the subject. In some aspects, the administration of the antibody, fragment thereof, or polynucleotides encoding the anti-MYCT1 antibodies described herein results in reduction of activity, function, expression and/or accumulation of MYCT1 by at least about 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to activity, function, expression and/or accumulation of MYCT1 before administration of the antibody, fragment thereof, or polynucleotides encoding the antibodies (baseline) or a control subject not receiving the treatment. [00247] In some aspects, the adminstration the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies reduces the tumor volume in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor volume before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment.

[00248] In some aspects, the adminstration the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies reduce the tumor volume in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor volume before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment. Tumor volume in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as X ray, CT scan, bone marrow biopsy, serum protein electrophoresis (SPEP), or MRI.

[00249] In some aspects, the adminstration of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies reduce the tumor angiogenesis in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor angiogenesis before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment. Tumor angiogenesis in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as counting the number of blood vessels in a given area using a stereomicroscope, or by measuring expression of biomarkers associated with angiogenesis including a _v [33 Integrin, endoglin, and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2.

[00250] In some aspects, the adminstration of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, may increase the immune response or anti-tumor immunity against cancer cells in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to immune response or anti-tumor immunity before administration of the antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), or a control subject not receiving the treatment. Immune response against cancer cells can be measured using biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, and density of tumor infiltrating lymphocyte (TIL).

[00251] In further aspects, the methods the disclosure may optionally comprise adminstration of one or more immune checkpoint inhibitor compounds. In some aspects, the immune checkpoint inhibitor compounds can be administered before, during or after the administration of disclosed antibodies, fragments thereof, or polynucleotides encoding the antibodies. In some aspects, immune checkpoint inhibitor may be an inhibitor of CTLA-4, PDL1 , PDL2, PD1 , B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, CSF-1 R, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK1 , CHK2, A2aR, CD28, CD86, CD69, CD48, CD113, CEACAM-1 , Galectin-1 , TIGIT, GPR56, CD48, GARP, PD1 H, LAIR1 , TIM1 , TIM4 and the B-7 family of ligands, or any combination thereof. In some aspects, the immune checkpoint inhibitors for methods herein comprise CTLA-4 blocking antibodies (Ipilimumab (Yervoy), Tremelimumab (Imjuno)), PD-1 inhibitors (Pembrolizumab (Keytruda), Nivolumab (Opdivo), Cemiplimab (Libtayo), CT- 011 (Pidilizumab), AMP224), PD-L1 inhibitors (Atezolizumab (tecentriq), Avelumab (Bavencio), Durvalumab (Imfinzi), BMS- 936559), Lag3 inhibitors (Relatlimab), combination of Lag3 and PD1 inhibitor (PD-1 inhibitor nivolumab (Opdualag) 0X40 inhibitor (MEDI6469), CD160 inhibitor (BY55). Non-limiting examples of inhibitors of CSF-1 R include PLX3397, PLX486, RG7155, AMG820, ARRY-382, FPA008, IMC-CS4, JNJ-40346527, MCS 110, or any combination thereof.

[00252] In certain aspects, the method may comprise administering one or more PD-1 inhibitor and/or PD-L1 inhibitor compounds. Non limiting examples of PD-1 inhibitor and/or PD-L1 inhibitor compounds include monoclonal antibodies that target either PD-1 or PD-L1 . In some aspects, monoclonal antibodies that target PD-1 or PD- L1 comprise Pembrolizumab, Nivolumab, Cemiplimab, Atezolizumab, Avelumab, Durvalumab, and/or Ipilimumab. [00253] In further aspects, methods are provided for cancer treatment in subjects who are insensitive or resistant to immune checkpoint inhibitor monotherapies. In such aspects, the subject is diagnosed as, or is suspected of having, or develops a cancer that is resistant or insensitive to an immune checkpoint inhibitor. In such aspects, the combination therapy disclosed herein has a greater than additive inhibition of tumor growth, which may be determined using any suitable measurement, nonlimiting examples of which include determining tumor volume. The combination therapy can be combined with any other, conventional cancer therapies, including but not limited to surgical and chemotherapeutic approaches.

[00254] In some aspects of the method, the combination of anti-MYCT 1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound is administered to a subject having a cancer that is initially sensitive to immune checkpoint inhibitor treatment and later becomes insensitive to immune checkpoint inhibitor treatment. In some aspects, the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may be administered to a subject having a cancer that is insensitive to immune checkpoint inhibitor treatment. In some aspects, the disclosed anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies sensitizes a cancer to immune checkpoint inhibitors.

[00255] In some aspects, adminstration of the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may reduce the tumor volume in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to tumor volume before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with immune checkpoint inhibitor compound (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving immune checkpoint inhibitor compound alone. In some aspects, adminstration of the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound reduces the tumor volume in a subject by at least 25%. Tumor volume in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as X ray, CT scan, bone marrow biopsy, serum protein electrophoresis (SPEP), or MRI.

[00256] In some aspects, adminstration of the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies with an immune checkpoint inhibitor compound reduce the tumor angiogenesis in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor angiogenesis before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving immune checkpoint inhibitor compound alone. Tumor angiogenesis in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as counting the number of blood vessels in a given area using a stereomicroscope, or by measuring expression of biomarkers associated with angiogenesis including a _v p3 Integrin, endoglin, and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2.

[00257] In some aspects, adminstration of the combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an immune checkpoint inhibitor compound may increase the immune response or antitumor immunity against cancer cells in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to immune response or anti-tumor immunity before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with immune checkpoint inhibitor compound (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving immune checkpoint inhibitor compound alone. Immune response against cancer cells can be measured using biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, and density of tumor infiltrating lymphocyte (TIL).

[00258] Still further, the method of treatment described herein may optionally comprise administering one or more VEGF inhibitors. In some aspects, the VEGF inhibitor can be administered before, during or after the administration of disclosed antibodies, fragments thereof, or polynucleotides encoding the antibodies. In non-limiting examples, a composition of the disclosure may optionally comprise one or more of axitinib, bevacizumab, cabozantinib, lapatinib, Lenvatinib, pazopanib, ponatinib, ramucirumab, ranibizumab, regorafenib, sorafenib, sunitinib and/or vandetanib.

[00259] In some aspects, the adminstration of the combination of anti- MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with a VEGF inhibitor may reduce the tumor volume in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to tumor volume before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with VEGF inhibitor (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving VEGF inhibitor alone. In some aspects, the adminstration of combination of anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with an VEGF inhibitor compound reduces the tumor volume in a subject by at least 25%. Tumor volume in a subject can be assessed using any conventional methods known in the art, non-limiting examples of which include, diagnostic techniques such as X ray, CT scan, bone marrow biopsy, serum protein electrophoresis (SPEP), or MRI.

[00260] In some aspects, the adminstration of the combination of anti- MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies with a VEGF inhibitor reduce the tumor angiogenesis in a subject by at least 10%, e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or above, as compared to tumor angiogenesis before administration of the anti-MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving a VEGF inhibitor alone. Tumor angiogenesis in a subject can be assessed using any conventional methods known in the art, nonlimiting examples of which include, diagnostic techniques such as counting the number of blood vessels in a given area using a stereomicroscope, or by measuring expression of biomarkers associated with angiogenesis including a _v ps Integrin, endoglin, and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2.

[00261] In some aspects, the adminstration of the combination of anti- MYCT1 antibodies, fragments thereof, or polynucleotides encoding the antibodies, with a VEGF inhibitor compound may increase the immune response or anti-tumor immunity against cancer cells in a subject by at least 10%, e.g., 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or above, as compared to immune response or anti-tumor immunity before administration of the combination antibodies, fragments thereof, or polynucleotides encoding the antibodies with a VEGF inhibitor (baseline), a control subject not receiving the treatment, or a subject receiving antibodies, fragments thereof, or polynucleotides encoding the antibodies alone, or receiving a VEGF inhibitor alone. Immune response against cancer cells can be measured using biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, and density of tumor infiltrating lymphocyte (TIL).

[00262] Among the various aspects of the present disclosure is the provision of methods for modulating MYCT1 activity. An aspect of the present disclosure provides for a method of regulating tumor angiogenesis (anti-angiogenesis, Myctl -targeted vascular control) and/or immunostimulation, which inhibit tumor growth, in a subject. In some aspects, the method comprises administering an anti-MYCT1 antibody to a subject having a cancer.

[00263] In further aspects the methods disclosed herein encompasses sensitizing a cancer to an immune checkpoint inhibitor in a subject. In such aspects the method comprises selecting a subject with a cancer, wherein the cancer is resistant to an immune checkpoint inhibitor. In some aspects, the subject may be diagnosed as, or is suspected of having, or develops a cancer that is resistant or insensitive to an immune checkpoint inhibitor, for e.g., by a physician. In further aspects, the method comprises administering to the subject an effective amount of a composition comprising an anti-MYCT1 antibody or a fragment thereof disclosed herein. In some aspects, the administration of the anti-MYCT1 antibody or fragment thereof in such subjects results in reduction in angiogenesis and increase in anti-tumor immunity in the subject. In further aspects, the administration of the anti-MYCT1 antibody in such subjects results in reduction of tumor volume.

[00264] Further aspects comprises a method of regulating tumor angiogenesis and/or increasing anti-tumor immunity in a subject. In such aspects, the method comprises administering to the subject a therapeutically effective amount of composition comprising an anti-MYCT1 antibody or fragment thereof.

[00265] In some aspects, the effective amount of an anti-MYCT1 antibody can be an amount effective to substantially block or inhibit MYCT1 expression and/or activity in cells. In some aspects, the effective amount of an anti-MYCT1 antibody can be an amount effective to substantially block or inhibit MYCT1 expression and/or activity endothelial cells (ECs). In some aspects, blocking MYCT1 in endothelial cells promotes an immunostimulatory microenvironment by enhancing CTLs infiltration and preventing CTLs apoptosis; contributes to an immunostimulatory microenvironment; leads to an anti-tumor microenvironment; and/or promotes endothelial regulation of tumor immunity. In some aspects, the effective amount of an anti-MYCT1 antibody can be an amount effective to reduce angiogenesis. In some aspects, the effective amount of an anti- MYCT1 antibody can be an amount effective to facilitate high endothelial venules (HEV) formation. In some aspects, administration of a composition of the present disclosure results in increased EC HEVs. In some aspects, after administration of an anti-MYCT1 antibody of the disclosure the subject has improved antitumor drug delivery and enhanced anti-tumor immunity. In some aspects, the subject has high endothelial venule formation and an antitumor immune environment, leading to a restricted tumor progression.

[00266] In some further aspects, the effective amount of an anti-MYCT1 antibody can be an amount effective to enhance robust CTL infiltration. In some aspects, the effective amount of an anti-MYCT1 antibody can be an amount effective to promote inflammatory M1 macrophage polarization. In some aspects, administration of a composition of the present disclosure results in reduced EC motility. In some aspects, administration of a composition of the present disclosure results deficient tumor vasculature. In some aspects, administration of a composition of the present disclosure results in the downregulation of the expression of Fas ligand in ECs.

[00267] In some aspects, the subject has upregulated MYCT1 in ECs prior to administration of the anti-MYCT1 antibodies. Suitable compositions, administration forms, dosing and dosing schedules for use in the methods of the present disclosure are disclosed herein, for instance those described in Section III which is incorporated by reference into this section.

[00268] In some aspects, the amount of an anti-MYCT1 antibdy and immune checkpoint inhibitor and/or VEGF inhibitor is an amount effective to reduce or prevent exhaustion of the infiltrating cytotoxic T lymphocytes (CTLs). In some aspects, combined vascular and immune control provides synergistic anti-tumor activity.

[00269] In another aspect, the disclosure provides a composition as disclosed herein for use in vitro, in vivo, or ex vivo.

[00270] Thus, in some aspects, the methods of the present disclosure are useful for reducing tumor or cancer progression or prolonging the survival of subject having a cancer or tumor. The present disclosure provides that combined vascular and immune control provide a synergistic anti-tumor activity. For example, targeting MYCT1 using an anti-MYCT1 antibody of the disclosure improves the response to anti-PD1 therapy in treatment-responsive and -refractory tumors and combined MYCT1 and VEGF targeting with anti-PD1 treatment produced a superior tumor control, suggesting synergy between MYCT1 and VEGF pathways.

[00271] In one aspects, this method generally includes the steps of providing a composition as described herein; administering the composition to a subject or cell (e.g. an endothelial cell).

[00272] In some aspects, the present disclosure provides a methods for treating tumors or cancer cells with increased risk of angiogenesis. In some aspects, the disclosure provides a method of treating a cancer or tumor by administering a composition of the disclosure sequentially or simultaneously with another cancer therapy. When administered sequentially the additional agent may be administered before or after the compound of the disclosure. In a preferred aspect, the additional agent is an immune check point blockade and optionally a anti-VEGF therapy.

[00273] In other aspects, compositions of the disclosure may be delivered to a cancer cell in vitro. A cancer cell may be a cancer cell line cultured in vitro. In some alternatives of the aspects, a cancer cell line may be a primary cell line that is not yet described. Methods of preparing a primary cancer cell line utilize standard techniques known to individuals skilled in the art. In other alternatives, a cancer cell line may be an established cancer cell line. A cancer cell line may be adherent or non-adherent, or a cell line may be grown under conditions that encourage adherent, non-adherent or organotypic growth using standard techniques known to individuals skilled in the art. A cancer cell line may be contact inhibited or non-contact inhibited.

[00274] In some aspects, the cancer cell line may be an established human cell line derived from a tumor. Non-limiting examples of cancer cell lines derived from a tumor may include the MM cell lines MM.1 S, H929, and RPMI, osteosarcoma cell lines 143B, CAL-72, G-292, HOS, KHOS, MG-63, Saos-2, or U-2 OS; the prostate cancer cell lines DU145, PC3 or Lncap; the breast cancer cell lines MCF-7, MDA-MB-438 or T47D; the myeloid leukemia cell line THP-1 , the glioblastoma cell line U87; the neuroblasto-ma cell line SHSY5Y; the bone cancer cell line Saos-2; the colon cancer cell lines WiDr, COLO 320DM, HT29, DLD-1 , COLO 205, COLO 201 , HCT-15, SW620, LoVo, SW403, SW403, SW1116, SW1463, SW837, SW948, SW1417, GPC-16, HCT-8, HCT 116, NCI-H716, NCI-H747, NCI-H508, NCI-H498, COLO 320HSR, SNU-C2A, LS 180, LS 174T, MOLT-4, LS513, LS1034, LS411 N, Hs 675.T, CO 88BV59-1 , CO88BV59H21 -2, Co88BV59H21-2V67-66, 1116-NS-19-9, TA 99, AS 33, TS 106, Caco-2, HT-29, SK-CO-1 , SNU-C2B or SW480; B16-F10, RAW264.7, the F8 cell line, or the pancreatic carcinoma cell line Panel .

[00275] Generally, the methods as described herein comprise administration of a therapeutically effective amount of a composition of the disclosure to a subject. The methods described herein are generally performed on a subject in need thereof.

[00276] The level of MYCT1 can be used as a predictive marker of the angiogenic status of a subject and therefore useful for making treatment decisions for subjects who can benefit from certain therapies (e.g. anti-angiogenics). For example, the level MYCT1 of a candidate subject can be compared with a reference value.

[00277] Therefore, the present disclosure also provides anti-MYCT1 antibodies conjugated to a detectable signal (i.e. a measurable substance, or a substance that generates a measurable signal). Non-limiting examples include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals using various positron emission tomographies, and nonradioactive paramagnetic metal ions. See, e.g., U.S. Pat. No. 4,741 ,900 for metal ions which can be conjugated to antibodies for use as diagnostics according to the disclosure. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, [3-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin; and examples of suitable radioactive material include ¹²⁵ l, ¹³¹ 1, ¹¹¹ In or "Tc. The signal generated by the agent can be measured, for example, by single-photon emission computed tomography (SPECT) or positron emission tomography (PET).

[00278] Anti-MYCT1 antibodies conjugated to a detectable signal may be used diagnostically to, for example, monitor the development or progression of a tumor or cancer as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment and/or prevention regimen. The patient's treatment can be adjusted based on the level of neurodegenerative disease progression.

[00279] In some aspects, a method of assessing disease progression in a subject being treated for a cancer or tumor is provided, the method comprising: (a) administering an anti-MYCT1 antibody disclosed herein that is labeled with an agent that generates a measurable signal as described herein (i.e. “labeled anti-MYCT1 antibody”), wherein the signal is measured in the patient following the administration; (b) administering the labeled anti-MYCT1 or antigen-binding fragment thereof at one or more time intervals following the administration of (a), wherein the signal is measured in the patient following the administration; and (c) assessing disease progression in the patient based on a change in the signal measured in the patient at the one or more time intervals following administration of (a); wherein an increase in the signal indicates progression of the neurodegenerative disease in the patient. In certain aspects, the subject is being treated with the same anti-MYCT1 antibody, but in an unlabeled form. In certain aspects, the subject is being treated with an anti-MYCT1 antibody that competitively inhibits the labeled anti-MYCT1 antibody binding to human ApoE. In certain aspects, the subject is being treated with an anti-MYCT 1 antibody that does not competitively inhibit the labeled anti-MYCT 1 antibody binding to human MYCT 1 . In certain aspects, the subject is being treated with other drugs known in the art.

[00280] In other aspects, a method of assessing disease progression in a subject being treated for a cancer or tumor is provided, the method comprising: (a) administering an anti-MYCT1 antibody disclosed herein that is labeled with an agent that generates a measurable signal as described herein (i.e. “labeled anti-MYCT1 antibody”), wherein the signal is measured in the patient following the administration; (b) assessing the disease state in the subject upon review of a comparison of the signal measured in the subject to the signal measured following administration of the labeled antibody or antigen-binding fragment thereof to one or more control subjects; wherein an increase in the signal generated in the patient relative to the control subject correlates with an increase in brain amyloid plaques; and (c) treating the patient with a therapy appropriate for the patient's disease state. A “control subject(s),” refers to any normal healthy subject (or a pool of subjects), a subject or subjects with different degrees of disease, or even the actual test subject at an earlier stage of disease.

[00281] A reference value may represent the same level of MYCT1 in a control subject or represent the level MYCT1 in a control population. In some examples, the same level MYCT1 in a control subject or a control population may be determined by the same method as used for determining the level MYCT1 in the candidate subject. In some instances, the control subject or control population may be a subject having cancer or a tumor or a subject population having cancer or a tumor who is responsive to treatment. In other instances, the control subject or control population may be a subject having cancer or a tumor or a subject population having cancer or a tumor who is non-responsive to treatment. Alternatively, the control subject or control population may refer to a healthy subject or healthy subject population. In a preferred aspects, the control subject or control population is of the same species (e.g., a human subject or human subject population) as the candidate subject. As used herein, assessing “responsiveness” or “non-responsiveness” to a therapy refers to the determination of the likelihood of a subject for responding or not responding to the therapeutic agent. For example, a responsive subject will have a therapeutic effect as a result of administration of an agent. In some aspects, a therapeutic effect includes to prevent or slow down (lessen) an undesired physiological change or disease/disorder. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e. , not worsening) state of disease, a delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), or can also mean prolonging survival as compared to expected survival if not receiving treatment or a non-responsive subject or population.

[00282] It is to be understood that the methods provided herein do not require that a reference value be measured every time a candidate subject is tested. Rather, in some aspects, it is contemplated that the reference value can be obtained and recorded and that any test level can be compared to such a reference level. The reference level may be a single-cutoff value or a range of values.

[00283] By comparing level of MYCT1 in a candidate subject as disclosed herein with a reference value as also described herein, the subject can be identified as responsive or likely to be responsive or as not responsive or not likely to be responsive to a therapy based on the assessing. [00284] For example, when the reference value represents the level of MYCT1 who are responsive to a therapy, derivation from such a reference value would indicate non-responsiveness to the therapy. In another aspect, when the reference value represents the level of MYCT1 who are responsive to a genotoxic therapy, about the same level of phosphorylation of MYCT1 in a candidate subject would indicate responsiveness to the therapy.

[00285] Alternatively, when the reference value represents the level MYCT 1 who are non-responsive to a therapy, derivation from such a reference value would indicate responsiveness to the therapy. In another aspect, when the reference value represents the level of MYCT1 who are non-responsive to a therapy, about the same level of MYCT1 in a candidate subject would indicate non-responsiveness to the therapy.

[00286] In some instances, derivation means that the level of MYCT1 (e.g., represented by a value) of a candidate subject is elevated or reduced as relative to a reference value, for example, by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 300%, 400%, 500% or more above or below the reference value.

[00287] Thus, the present disclosure provides a method for assessing responsiveness to a therapy or detecting the angiogenic status of a cancer or tumor in a subject having a cancer or tumor. In one aspect, a method for assessing responsiveness to a therapy or detecting the angiogenic status may comprises (a) providing a biological sample obtained from a subject and measuring, in the cancer cell or tumor cell or endothelial cell of the sample, the level of MYCT 1 ; and (b) determining the subjects responsive-ness to the therapy or angiogenic status when the measured MYCT 1 level deviates from a reference value.

[00288] MYCT1 levels may be used in various mathematical operations to assess responsiveness or angiogenic status. For instance, MYCT1 values can be used in various statistical models (e.g., linear regressions, LME curves, LOESS curves, etc.) in conjunction with other known biomarkers. Selection of measurements and choice of mathematical operations may be optimized to maximize specificity of the method. For instance, diagnostic accuracy may be evaluated by area under the ROC curve and in some aspects, an ROC AUC value of 0.7 or greater is set as a threshold (e.g., 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, etc.).

V. Kits

[00289] The present disclosure provides kits comprising one or more anti- MYCT1 antibodies, fragment thereof, or polynucleotides encoding the antibodies for use with a method of the disclosure. The kits may comprise a composition comprising a anti-MYCT1 antibody, fragment thereof, or polynucleotide encoding the antibody or a pharmaceutical composition thereof, and instructions for administering the antibody fragment thereof, or polynucleotide encoding the antibody or a pharmaceutical composition thereof to a subject in need thereof. The kit can further comprise immune cell inhibitor and/or VEGF inhibitor that can be administered in combination with the anti-MYCT1 antibody, fragment thereof, or polynucleotide encoding the antibody. In some aspects, the kits can further comprise a sterile, pharmaceutically acceptable carrier, buffer or other diluent. The kits provided herein generally include instructions for carrying out the methods. Instructions included in the kits may be affixed to packaging material or may be included as a package insert. While the instructions are typically written or printed materials, they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this disclosure. Such media include, but are not limited to, electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. As used herein, the term “instructions” may include the address of an internet site that provides the instructions.

[00290] The disclosed kits may have a single container that contains the disclosed anti-MYCT1 antibody, fragment thereof, or polynucleotide encoding the antibody with or without any additional components, or they may have distinct containers for each desired agent. Where combined therapeutics are provided, a single solution may be pre-mixed, either in a molar equivalent combination, or with one component in excess of the other. Alternatively, each of the antibody, fragment thereof, or polynucleotide encoding the antibody and other anti-cancer agent components of the kit may be maintained separately within distinct containers prior to administration to a patient.

[00291] When the components of the kit are provided in one or more liquid solutions, the liquid solution is preferably an aqueous solution, with a sterile aqueous solution being particularly preferred. However, the components of the kit may be provided as dried powder(s). When reagents or components are provided as a dry powder, the powder can be reconstituted by the addition of a suitable solvent. It is envisioned that the solvent may also be provided in another container.

[00292] The containers of the kit will generally include at least one vial, test tube, flask, bottle, syringe or other container means, into which the disclosed anti- MYCT1 antibody, fragment thereof, or polynucleotide encoding the antibody, and any other desired agent, may be placed and, preferably, suitably aliquoted. Where separate components are included, the kit will also generally contain a second vial or other container into which these are placed, enabling the administration of separated designed doses. The kits may also comprise a second/third container means for containing a sterile, pharmaceutically acceptable buffer or other diluent.

[00293] The kits may also contain a means by which to administer the disclosed anti-MYCT1 antibody, fragment thereof, or polynucleotide encoding the antibody to an animal or patient, e.g., one or more needles or syringes, or even an eye dropper, pipette, or other such like apparatus, from which the formulation may be injected into the animal or applied to a diseased area of the body. The kits of the present invention will also typically include a means for containing the vials, or such like, and other component, in close confinement for commercial sale, such as, e.g., injection or blow-molded plastic containers into which the desired vials and other apparatus are placed and retained.

[00294] As various changes could be made in the above-described materials and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and in the examples given below, shall be interpreted as illustrative and not in a limiting sense. EXAMPLES

[00295] The following examples are included to demonstrate various aspects of the present disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific aspects which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

Materials and Methods

Table 2: Preparation of 120 medium

Hybridoma line culture

[00296] The following reagents were used for preparing media as shown in

Table 3

Table 3: Media for Hybridoma line culture

[00297] The cells were maintained in the media at about 1 x10 ⁵ cells/ml to

1 x10 ⁶ cells/ml.

EC culture

[00298] MCEC and its derivatives: MCEC cells were made from FVB/N mice hearts from mice having MHC haplotype "q." The culture media was prepared using DMEM high Glucose 10% FBS, l Ommol/L Pen-Strep, and l Ommol/L HEPES. Gelatin pre-coating is recommended for this cell line but is not required. Cell doubling time was approximately 30h. The cells were sub-cultured at a passage ratio of approximately 1 :6. Cryopreservation of cells were undertaken in 10% DMSO in FBS at 1 .5 million cells/ml.

[00299] MLEC, MLEC Myctl KO, Myctl KO MLEC overexpressinq human short MYCT1 or long MYCT1, and its derivatives: iMLEC and iMLEC Myctl KO cells were made from WT and Cdh5-cre Myctl f/f C57/B6 mice lungs, respectively. The cells were immortalized by DOX inducible SV40 T with Puromycin and Blasticidin selection (pLV[Tet]-TRE3G>SV40-T(ns):T2A:Puro and pLV[Exp]-Bsd-{mCd144}>Tet3 constructs). Culture media was prepared using DMEM high Glucose 10% FBS, 10mmol/L Pen-Strep, 10mmol/L HEPES, and DOX (40ng/ml). 0.1 % Gelatin (in dH2O) coating (30min at 37C incubator»aspiration»Drying in the TC hood for 30min»ready to use) of the culture vessel is required for optimal growth. The cells take about 3-4 days to completely repopulate the culture vessel after a passage. Sub-culture was done at about 1 :3 splitting ratio. Cryopreservation was performed using 10% DMSO in FBS at 1 .5 million cells/ml. [00300] HUVEC, MYCT1 knock-down HUVEC, MYCT1 knock-down HUVEC overexpressing mouse Myctl: The HUVEC cells were purchased through Fisher (Catalog No.08-774-388). Human TERT lentivirus (vector: LB12_FLAG_TERT_pCDH_MCS_EF1_NEO) was used to immortalize HUVEC cells, followed by G418 selection. Endothelial Cell Growth Medium (Ready-to-use) (Promo cell, Cat: C-22010), a ready-to-use media with about 2% FBS with additional serum to make it up to 10% was used as culture media. 0.1 % Gelatin (in dH2O) coating (30m in at 37 °C incubator»aspiration»Drying in the TC hood for 30 min»ready to use) of the culture vessel was required for optimal growth. The cells take about 4-5 days to repopulate the culture vessel completely after a passage. Passaging was performed at 1 :2 splitting ratio. It was observed that HUVEC cells like to stay close to each other and if the cells are seeded or passaged sparsely, they might not grow at all. Cryopreservation was performed at 10% DMSO in FBS at 1.5 million cells/ml.

[00301] The HUVEC MYCT1 KD cell line was developed by transducing HUVEC cell line with MYCT1 shRNA lentiviral particles followed by puromycin selection. HUVEC MYCT1 KD Myctl overexpressing line was generated by further transducing the iHUVEC MYCT1 KD cell line with Myctl overexpressing lentiviral particles followed by blasticidin selection.

Endothelial Tube Formation Assay

[00302] The endothelial cells were serum starved overnight. The following day, p-Slide Angiogenesis plates (Cat: 81506, ibidi) were coated with Matrigel (Cat: 96992, Corning) (1 Opl/well) and incubated at 37°C for 30-45minutes until the Matrigel is polymerized. The overnight serum-starved endothelial cells were plated on the Matrigel- coated plates as 8,000 cells/well with 50pl culture media on top. The plates were incubated at 37°C for 6-8 hours before taking pictures with a microscope. Angiogenesis analyzer module of ImageJ software (NIH) was used to quantify total tube length, number of loops, and number of branches. Endothelial sprouting assay

[00303] The following reagents are used in the endothelial sprouting assay. 1 . EGM-2 BulletKit (containing FGF2 and VEGF-A; Lonza, cat. no. CC-3162)

2. M199

3. DMEM High Glucose

4. Fetal bovine serum

5. HBSS

6. Ca2+ and Mg2+ free Dulbecco’s Phosphate Buffered Saline (DPBS; Life Technologies, cat. no. 14190-094)

7. Cytodex 3 microcarrier beads (GE Healthcare, cat. no. 17-0485-01 )

8. Fibrinogen type I from bovine plasma (Sigma-Aldrich, cat. no. F8630)

9. Thrombin from bovine plasma (Sigma-Aldrich, cat. no. T3399)

10. Aprotinin from bovine lung (Sigma-Aldrich, cat. no. A1153)

11 . Trypsin/EDTA, UV-inactivated (PAA Laboratories, cat. no. L11 -660)

12. 5ml, 15ml, and 50ml Polypropylene tube

13. 5ml polystyrene tube (FACS tubes)

14. Low binding Eppendorf tube (1 ,5ml)

15. PKH kits

16. 24-WELL glass bottom plate with #1 .5 coverglass

17. Cell counting kits

[00304] Endothelial growth medium (EGM-2) was prepared and supplemented according to the supplier’s instructions before use.

[00305] Fibroblast growth medium was prepared with DMEM with 10% FBS). The DMEM was supplemented with 10% FBS before use.

[00306] Endothelial cells (YSE/MCEC cells) were grown to about 80% confluency in EGM-2 before starting the assay.

[00307] Fibroblasts (NIH3T3 cells) were grown in fibroblast growth medium to about 80% confluency.

[00308] Microcarrier beads: 1g Cytodex3 microcamers (3x10 ^A 6 beads) were swollen and hydrated in Ca ²⁺ and Mg ²⁺ free PBS 50ml for at least 3 h at room temperature. The supernatant was decanted and the microcarriers were washed for a few minutes in fresh Ca ²⁺ and Mg ²⁺ free PBS (30-50 ml). The PBS was discarded and replaced with fresh Ca ²⁺ and Mg ²⁺ free PBS (30-50 ml/g and the microcarriers were sterilized by autoclaving (115 °C, 15 min, 15 psi). The pH of all solutions was adjusted to 7.4. When hydrating Cytodex 3, initial surface tension may occasionally prevent wetting and sedimentation of the microcarriers. Should this occur, Tween 80 can be added to the PBS used for the first hydration rinse (2-3 drops Tween 80/100 ml PBS).

[00309] Thrombin solution: Thrombin was dissolved at 50 ll/rnl in DPBS. Aliquots of 0.5 ml each were made. Aliquots can be stored at -20 °C. Avoid repeated freezing and thawing.

[00310] Aprotinin solution: Aprotinin was dissolved at 4 ll/rnl in ddH2O. The solution was sterile filtered and aliquots of 0.5 ml each were made. Aliquots can be stored at -20 °C.

[00311] The endothelial sprouting assay was performed as using the following procedure.

[00312] Step 0: Preparing cells [4-5 days]

0.1 Bring up different types of YSE/MCEC cells and NIH3T3 cells in 10%FBS M199 1 %P/S and 10%FBS DMEM 1 mM l-glutamine 1 %P/S medium, respectively.

0.2 Switch medium to EGM-2 the day before beading for YSE/MCEC cells (Day 0).

[00313] Step 1 : Prepare NIH3T3 fibroblasts (Day 1) [10 minutes]

1 . Remove and discard the culture media from T75 flask with ~80% confluent NIH3T3 cells, and replace with pre-warmed EGM-2. Incubate overnight at 37 °C, 5% CO2 in a cell culture incubator.

[00314] Step 2: Prepare different endothelial cells (Day 1) [35 minutes]

These processes are to be done separately for all types of YSE/MCEC cells:

2.1 Harvest 80% confluent YSE/MCEC cells from T75 flask by removing the media, rinsing with pre-warmed trypsin-EDTA, adding 3 ml of trypsin-EDTA and incubating at 37 °C for couple of minutes to loosen the cells. Briefly tap the side of the flask to fully detach the cells. Add 12 ml EGM-2, gently pipette the solution up and down, and transfer the cell suspension into a sterile 50 ml conical polypropylene tube.

2.2 Count the cells by transferring 10pl of the cell suspension into a counting chamber or a hemocytometer. Centrifuge the cells at 400g for 5 min. Aspirate and discard the supernatant and resuspend the cells in HBSS at a concentration of 2.5x10 ⁶ /m I. Reserve on ice.

2.3 Take 1 ml of the HBSS-cell suspension to a new 5ml polypropylene tube and add 3ml more HBSS. Centrifuge the cells at 400g for 5 min, aspirate and discard the supernatant (leaving <25pl). As a result, starting cell number is 2.5x10 ⁶

[00315] Step 3 (Optional): Membrane Labeling with PKH26 or PKH67 or CellVue dyes (Day 1) [25 minutes]

These processes are to be done separately for all types of YSE/MCEC cells:

3.1 During the last cell washing in step 2.3, add 250pl of Diluent C (from the PKH kits) to a 5m I polypropylene tube.

3.2 Add 250pl of Diluent C to the washed cell pellet from Step 1 .3 and mix with pipette 3-4 times to obtain a single cell suspension (2x cells).

3.3 Prepare a 2x (4pM) dye solution by adding 1 pl of 1 mM PKH26/67/CellVue dye stock in ethanol (from the PKH kit) to the 250pl Diluent C tube prepared in Step 3.1 and vortex to disperse uniformly.

3.4 Immediately pipette the 2x cell suspension from Step 3.2 into this 2x dye solution and pipette up & down 3-4 times to completely disperse the cells in dye. Total incubation time is 1-2minutes.

3.5 Add 500pl (equal volume) of heat inactivated FBS to stop dye uptake. If complete medium is used instead, use 5ml of 10%FBS medium or as appropriate. Centrifuge the cells at 400g for 5 min. Resuspend the cells in 5ml EGM-2, and transfer to a 15ml tube. Again, centrifuge at 400g for 5 min, resuspend in 5ml EGM-2, and centrifuge at 400g for 5 min. Finally, resuspend in 5m I EGM-2 at a cone, of 5 x 105 cells/ml. [00316] Step 4: Bead coating (Day 1) [4 hours 15 minutes]

For all 24 wells of a 24-well plate:

4.1 Take 10OpI of microcarrier bead suspension (containing 6000 beads approx.) into a 5ml round-bottom polystyrene tube (FACS tube) and add 3 ml EGM-2. Let the beads sediment without shaking the tube (~2-3min). Carefully aspirate the supernatant by pipette, leaving about 0.5 ml EGM-2 in the tube.

4.2 Add 4.8 ml (2.4 x 1 o ⁶ cells) of the cell suspension prepared in step 3.5 to the beads, close the lid halfway and shake well, but without inverting the tube. This results in -400 cells/bead. Place the bead-cell suspension into the incubator at 37 °C, 5% CO2. Shake the tube every 20 min for 4h, taking care to raise all sedimented beads.

4.3 Transfer the coated beads into two (2) T25 cm ² flask with additional 7 ml EGM-2 (resultant 6ml/T25). Observe the coated beads under a low magnification microscope. They should have a golf ball-like appearance, with ECs homogenously covering the bead surface. Incubate overnight (10-12h) at 37 °C, 5% CO2.

[00317] Step 5: Embedding cell-coated beads into fibrin gels in a 24- well plate (Day 2) [1 hour 45 minutes]

5.1 Add 35mg fibrinogen to 14ml of DPBS in a 50ml tube to prepare a

2.5 mg/ml fibrinogen solution. A total volume of 12 ml is required per 24-well plate (500pl per well). Incubate at 37 °C for 20 min to dissolve. Filter with 0.45pm syringe filter. Transfer 12ml of this filtered solution to new sterile 50ml polypropylene tube.

5.2 Thaw a 0.5ml aliquot of Thrombin and Aprotinin solution each.

5.3 Add 450pl Aprotinin solution (made as 4U/ml; applicable cone. 0.15U/ml) to 12ml of the fibrinogen solution.

5.4 Transfer the EC-coated beads into a sterile 50 ml polypropylene tube. Rinse the flasks with 5 ml EGM-2 each and transfer to the same tube to recover as many beads as possible. 5.5 Let the beads sediment for about 3 min, then very carefully aspirate and discard the supernatant, leaving ~1ml in the tube to avoid aspirating beads. Resuspend the beads very carefully with pipetting slowly and transfer this ~1 ml suspension to a 1 ,5ml Low binding Eppendorf tube. Let it settle down for ~3 minutes.

5.6 Wash the beads by adding 1 ml of pre-warmed EGM-2. Let the beads sediment again for about 3 min, then very carefully aspirate and discard the supernatant, leaving as little growth medium as possible covering the beads.

5.7 Repeat step 5. Before sedimentation, take 10pl (in duplicate) of this beadcell suspension on a large coverslip, count bead number under microscope, and calculate the average bead number.

5.8 Add 1 ml of the fibrinogen solution to the beads and mix carefully. Transfer this suspension to the rest of the 11 ml fibrinogen solution and mix carefully.

5.9 Using a multi-step pipette, transfer 20pl of thrombin solution (made as 50U/ml; applicable cone. 2U/ml) into the center of each of the 24 wells of the 24- well plate. (Total 480pl). Other studies also reported using 12.5pl (for applicable cone. 0.625U/ml) and 40pl (for applicable cone. 4U/ml)

5.10 Mix the cell-bead-fibrinogen suspension slowly and transfer 500pl of the bead-fibrinogen suspension directly into the thrombin solution in each of the 24 wells of the plate. Mix with the thrombin gently by pipetting 4-5 times. Avoid moving the plate, pipetting fast, and creating bubbles. Change pipette tips for every well.

5.11 Let the gels solidify for about 5 min at room temperature, then keep them at 37°C to avoid damage to the endothelial cells (roughly around 20-25 minutes).

5.12 In the meantime, harvest NIH3T3 cells by removing the media, rinsing with pre-warmed trypsin-EDTA, adding 2 ml of trypsin-EDTA (for a 25 cm ² flask) and incubating at 37°C for couple of minutes to release the cells. Briefly tap the side of the flask to fully detach the cells. Add 5 ml EGM-2, gently pipette the cell suspension up and down, and transfer it into a sterile 15 ml PP tube. 5.13 Count the cells by transferring 10 pl of the cell suspension into a counting chamber or a hemocytometer. Centrifuge the cells at 400g for 5 min in a centrifuge. Aspirate and discard the supernatant and resuspend the cells in EGM-2 at a concentration of 1x10 ^A 6 cells per 1 ml.

5.14 After the gels are formed, add 1 ml of EGM-2 dropwise and very slowly to each of the wells.

5.15 Distribute the NIH3T3 cell suspension carefully onto the polymerized fibrin gels by pipetting 20pl (~20,000 cells) per well. Change tips for every well.

5.16 Incubate overnight at 37 °C, 5% CO2.

[00318] Step 6: Sprout initiation (TIMING VARIABLE: ~24h-8d)

6. 1 Change growth medium every other day. Carefully aspirate the medium above the fibrin gel, leaving only a small amount of liquid covering the gel. Refill each well with a suitable amount of pre-warmed EGM-2. Incubate at 37 °C, 5% CO2.

6.2 Monitor the progress of sprouting using a bright-field microscope.

6. 3 Examine the sprouting under confocal microscope.

Endothelial Scratch Assay (Wound Closure Assay)

[00319] 50,000 endothelial cells/well of 24-well plate were seeded with

500pl of cell culture media. The plates were incubated at 37°C for ~8 hours. The endothelial cells were serum starved overnight. A scratch was made on the monolayer of the endothelial cells with a 200pl pipette in the morning the next day. The media was replaced with 0.5% serum containing media. Picture was taken with a microscope at Oh. The gap closure was tracked for 24h or until closed with a microscope.

ELISA assay

[00320] The following reagents prepared for use in ELISA assay as described below.

[00321] ELISA coating buffer: Add 1 .59 g Sodium Carbonate (Na2CO3, Fisher # S263) and 2.93 g Sodium Bicarbonate (NaHCO3, Fisher # S233) to 900ml in MilliQ or dH2O. Bring the pH to 9.6 (indirect assay) or to 8.8 (direct assay to bind IFN gamma). Bring to 1 L in MilliQ or dH2O or store at 4°C.

[00322] ABTS (ELISA Substrate Buffer) 1L: Dissolve 12.8g Citric Acid Monohydrate (C6H8O7.H2O, Sigma # C1909) and 12.8g Sodium Phosphate Dibasic (Na2HPO4, Sigma # S0876) in 800ml MilliQ or dH2O, adjust pH to 4.2, add 0.548g ABTS (C18H24N6O6S4, CAS # 30931 -67-0 Sigma # A1888) and bring up to 1 L with MilliQ or dH2O. The buffer can be aliquoted (11 ml used per plate) and store at -20°C. Immediately before applying to ELISA plate, add (1000X) of 30% H2O2 and combine (for e.g., 11 ml ABTS + 11 pl Hydrogen Peroxide). The buffer is added at 10Opl/well.

[00323] ELISA Wash Buffer (10X) 2L: Add 121 .2 g Trizma-HCI (C4H11 NO3 HCI, Sigma # T-3253) and 27.8 g Trizma Base (C4H11 NO3, Sigma # T-1503) to 1800ml in MilliQ or dH2O. Adjust pH to 7.6. Add 40ml of Triton X-100 (Sigma # X100) and bring up to 2L in MilliQ or dH2O. The buffer is used at 1X dilution.

[00324] The ELISA assay was performed using the following procedure.

1. Coat Thermo Immulon II 96-well ELISA plates with 100ul/well of Antigen (1 - 3ug/ml) diluted in Carbonate buffer.(pH 9.6) Thermo # 3455. Seal and incubate 2 hours at 37°C or O/N at 4°C. Do not use parafilm at 37°C.

2. Wash plates 8x in 1X ELISA Wash Buffer using the “dunking” method. Flick and blot dry.

3. Add 100pl/well of Supernatants from plates (1 ° Ab). Add 10OpI of Media Only to wells H11 an H12 to serve as negative controls. Wells H9 and H10 will receive a known positive control, (Terminal bleed serum at 1 : 1000). If screening a subcloned line, include 10OpI of SN from the parental line in wells H7-8

4. Incubate 2-4 hours at room temperature and overnight at 4°C. (Optimal for screenings of Parental plates)

5. Wash plates 8 times in 1X ELISA Wash Buffer and blot dry.

6. Add 100pl/well of peroxidase conjugated 2° Ab (Peroxidase Goat anti-Mouse IgG Gamma-chain specific Jackson Immuno Research #115-035-071 , Each lot should be titered for low background and high signal) at a dilution of 1 :5000

7. Incubate 1 hour @ RT. 8. Thaw ABTS (substrate). Will require 11ml per plate.

9. Wash 8 times in 1X ELISA Buffer and blot dry.

10. Add 1 OOpl/well of substrate (ABTS + 0.1 % H2O2). Add 11 pl 30% Hydrogen Peroxide to 11 ml of ABTS solution per plate.

11 . Allow color to develop 10-20 minutes and immediately read on the Synergy HI plate reader (A 414nm - green) using the Gen5 program.

Method of Analysis

[00325] Tube Formation assay. Tube formation in 3 randomized microscopic images in each condition was counted as tube loop and branch per microscopic field using Image! Data is shown as the mean values ± SD from a representative 5 results.

[00326] Fibrin gel bead sprouting angiogenesis assay: Beads in 3 randomized microscopic images in each condition were counted sprout number and length per bead were quantified using Image! Data is shown as the mean values ± SD from a representative 5 beads results.

[00327] Scratch assay: Wound distance in 3 randomized microscopic fields was measured in each condition and calculated relative wound closure using Image! Relative wound closure was calculated as shown below:

Relative Wound Closure (%) = (Initial wound distance-Closured wound distance)/lnitial wound distance X 100

[00328] Data is shown as the mean values ± SD from a representative 5 results.

[00329] Statistical analysis: All statistical analyses were conducted using GraphPad Prism (Version 9.0; LaJolla, CA). Data are presented as mean ± standard deviation (SD). Statistical comparisons between groups were performed using a oneway ANOVA or two-way ANOVA. P-values less than 0.05 were considered statically significant. *p<0.05, **p<0.01 , ***p<0.001 and ****p<0.0001 .

Example 1: Generation and Characterization ofAnti-MYCT1 Blocking Antibodies [00330] Anti-MYCT1 blocking antibodies were generated using two independent fusion proteins. FIG. 1B shows the immunization scheme to generate MYCT1 monoclonal antibodies disclosed herein. Myctl knockout (KO) mice were immunized with pcDNA3.1 -Myctl (FIG. 2A) or MYCTI 1-19 -LS polypeptide, followed by booster injections using MYCTI 1-19-KLH. An exemplary MycT1 Terminal Sera titration from two immunized animals is further provided in FIG. 1C-1 D. MYCT11-19 comprises amino acids with 100% sequence identity to amino acids 48-67 of human MYCT1 protein isoform 1 , amino acids 1-19 of human MYCT1 isoform 2, and 1 -19 of mouse MYCT1 protein (FIG. 1A). ELISA assay with MYCT11-19-BSA, Fluorescence-activated cell sorting (FACS) using Myctl knocked-down or over-expressing endothelial cells, as well as scratch assay were used to screen generated MYCT1 antibodies (FIG. 3A-3D). FIG. 4A-FIG. 4C show results from FACS and scratch assay of antibodies obtained using pcDNA3.1 -Myctl immunization.

[00331] Inventors ran multiple assays, an exemplary first round of ELISA run and results from which are provided in Table 4. A list of first round of subclones identified are provided in Table 5.

Table 4: Results from an exemplary ELISA run positive controls: (sera) Wells H9-10 negative controls (media) Wells H1 1 -12

1 g/ml MycT1 antigen

Original Fusion plates (1 -12)

Secondary Ab: Px IgG @ 1 :5000 [00332] Spleen from one immunized mouse (immunized with pcDNA3.1 - Myctl ) that had highest ELISA titer, good FACS staining, and blocking function in scratch assay was further subjected to ELISA using MYCTT- - BSA, FACS, and scratch assay. 15 clones were identified that had IgG characteristics (Table 5) and greater than 60 lines were identified as having IgM characteristics. Further screening using ELISA using MYCTI 1-19- BSA, FACS, and scratch assay were undertaken. The inventors took raw data from these assays and identified 5 clones. These 5 clones were further subjected to screening and two clones 2B4, lgG2b (100% clonal) 11 B6, lgG1 (98% clonal) were identified (FIG. 5A). Further, two subclones of 2B4, 2B4F9D9, and 2B4F9D3 were identified. These clones were subjected to further analysis, and were purified and sequenced. An exemplary second round of ELISA run and results are provided in Table 6A-6B. Similar method was used for identification of other clones from sera from a second mice including 3E3, 8D12, 9E2 and 9F8 (FIG. 5B). The exemplary first ELISA run and results are provided in Table 6C-6D. Exemplary results from isotyping experiments of clones 2B4F9D9, 2B4F9D3, 8D2.C12, and

11 B6.G10.C12 using ELISA are shown in Tables 6E-6F. Table 6I shows the isotype identified for the antibody clones.

Table 5: Hybridoma Lines Banked, first round of subclones

Table 6A: Representative ELISA run with antibody clone 2B4.F9

Parental SN : Wells H7-8 positive controls: (sera) Wells H9-10 negative controls (media) Wells H1 1 -12

1 pg/ml MycT1 antigen coated plates

Secondary Ab: Px Goat anti-Mouse IgG, Fcg @ 1 :5000

Table 6B: Representative ELISA run with antibody clone 11B6.G10

Parental SN : Wells H7-8 positive controls: (sera) Wells H9-10 negative controls (media) Wells H1 1 -12

1 pg/ml MycT1 antigen coated plates

Secondary Ab: Px Goat anti-Mouse IgG, Fcg @ 1 :5000 Table 6C: Representative ELISA run with antibody clone 9E2A parental line SN Wells H8-9 positive controls: (sera) Wells H9-10 negative controls (media) Wells H1 1 -12 1 pg/ml MycT1 antigen coated plates

Secondary Ab: Px Goat anti-Mouse IgG, Fcg @ 1 :5000 parental line SN Wells H8-9 positive controls: (sera) Wells H9-10 negative controls (media) Wells H1 1 -12 1 pg/ml MycT1 antigen coated plates

Secondary Ab: Px Goat anti-Mouse IgG, Fcg @ 1 :5000

Table 6E: Isotyping of antibody clones 2B4.F9.D9 and 2B4.F9.D3 (MycT-1 coated plate)

Supernatant samples diluted 1 :1 (2.4ml total in media). Purified Ab samples diluted (in 1 -10) to 10pg/ml. 10Oul per well = 800pl total per row.

Table 6F: Isotyping of antibody clones 8D2.C12 and 11B6.G10.C12 (MycT-1 coated plate)

Supernatant samples diluted 1 :1 (2.4ml total in media). Purified Ab samples diluted (in 1 -10) to 10pg/ml. 10Oul per well = 800pl total per row.

Table 6G: Isotyping of antibody clones 2B4.F9.D9 and 2B4.F9.D3 (kappa coated plate)

Supernatant samples diluted 1 :1 (2.4ml total in media). Purified Ab samples diluted (in 1 -10) to 10pg/ml. 10Oul per well = 800pl total per row.

Table: 6H: Isotyping of antibody clones 8D2.C12 and 11B6.G10.C12 (kappa coated plates)

Supernatant samples diluted 1 :1 (2.4ml total in media). Purified Ab samples diluted (in 1 -10) to 10pg/ml. 10Oul per well = 800pl total per row.

Table 61: Isotype of antibody clones

[00333] The clones were further purified and sequenced to identify the sequences of the variable domains. The sequences of the clones are listed in Table 7. Further, chimeric MYCT1 antibodies using the 2B4 or 11 B6 variable region and human lgG1 constant region can also be generated. Table 7: Sequences of identified clones.

[00334] Clone 2B4F9D9 was further characterized using FACS, and scratch assay. FACS using hybridoma supernatant containing candidate antibody 2B4 in overexpressing (HA-mMOE) murine cardiac endothelial cell (MCEC) is shown in FIG. 6A. Scratch assay show that hybridoma supernatant containing candidate antibody 2B4F9D9 had reduced wound closure (FIG. 6B-FIG. 6B), indicating defective migratory properties in the angiogenic environment.

Example 2: In vitro assays for characterization of identified MYCT1 antibodies

[00335] In vitro angiogenic assays include fibrin gel bead sprouting assay, tube formation assay, and wound healing or scratch assay.

[00336] Sprouting assay was performed using inducible Murine Lung Endothelial Cell (iMLEC) treated with purified antibody clones 11 B6, 2B4F9D3 and IgG as a control, at 32 pg/well for 15 hours. Further and iMLEC Mytd KO cells were treated with IgG was used as a control. As shown in FIG. 7A-7C, sprouts per bead and sprouting length was significantly reduced in iMLEC cells treated with the antibody clones and in iMLEC Mytd KO cells treated with IgG. Similarly, sprouting assay performed in Murine Cardiac Endothelial cell (MCEC) treated with 11 B6 and 2B4F9D3 showed significant reductions in sprouts per bead and sprouting length (FIG. 8A-8C, Table 8A). Sprouting assay conducted in purified antibody clones 3EC12, 8D2C12 and 9E2H5 in MCEC cells for 30 hours, showed significant reductions in sprouts per bead and sprouting length comparable to antibody clone 2B4 (FIG. 9A-9C). Further, inducible human umbilical vein endothelial cells (iHUVEC) treated at increasing concentrations at 20pg/well, 40pg/well, and 80pg/well of 11 B6 or 2B4F9D3 for 24 hours (FIG. 9D, FIG. 9F, Table 8B-8C) and 48 hours (FIG. 9E, FIG. 9G, Table 8D-8E) were observed to have dose dependent reduction in sprouting. This suggested that the disclosed antibody clones had MYCT1 neutralizing activity in human endothelial cells.

Table 8A: Length of sprout in MCEC cells during sprouting assay.

Table 8B: Number of sprouts in iHUVEC cells at 24 hours during sprouting assay.

Table 8C: Length of sprouts in iHUVEC cells at 24 hours during sprouting assay.

Table 8D: Number of sprouts in iHUVEC cells at 48 hours during sprouting assay.

Table 8E: Length of sprouts in iHUVEC cells at 48 hours during sprouting assay. [00337] Tube formation assay was further performed to characterize the purified antibodies. FIG. 10A shows representative images of tube formation in iMLEC cells treated with 11 B6 and 2B4F9D3 for 4 hours at 4pg/well. 11 B6 and 2B4F9D3 greatly reduced tube formation in treated cells. Significant reductions in tube formations were also observed in in MCEC cells treated with 2B4F9D3, 3EC12, and 8D2C12 (FIG. 10B-10C, Table 8F). Antibody clone 9E2H5 showed slight but statistically nonsignificant reduction in tube formation (FIG. 10C). Additionally, a dose dependent reduction in tube formation was observed in iHUVEC cells treated with increasing concentrations of 11 B6 or 2B4F9D3 (8pg/well, 16pg/well, and 32pg/well) for 16 hours (FIG. 10D, Table 8F-8H). There were significant reductions in loop and branch number observed in cells treated with 32pg/well of antibodies, indicating that disclosed antibodies have MYCT1 inhibitory activity in human endothelial cells.

Table 8F: Number of loop in MCEC cells during tube formation assay.

Table 8G: Number of loop in iHUVEC cells at 24 hours during tube formation assay.

Table 8H: Number of branches in iHUVEC cells at 48 hours during tube formation assay.

[00338] Hybridoma supernatant containing antibody clone were further tested using scratch assay. As shown in FIG. 11A-11B MCEC cells treated with 32 pg/well of hybridoma supernatants of 11 B6 or 2B4F9D3 showed significantly less wound closure, compared IgG treated cells. Similarly, iMLEC cells treated with hybridoma supernatants of 11 B6 or 2B4F9D3 added at 32 pg/well and iMLEC MKO cells showed reduced wound closure (FIG. 11C-11D). Hybridoma supernatants of 3E3C12, 8D2C12, 9E2H5, or 2B4F9D3 added at 50pg/well showed similar reductions in wound closure (FIG. 11E-11F, Table 8I).

Table 8I: Wound closure in MCEC cells during scratch assay.

[00339] These results show that the treatment with identified antibody clones of MYCT1 reduced angiogenesis.

Example 3: Combined MYCT1 antibody and a-PD1 antibody treatment can inhibit tumor growth in vivo.

[00340] MYCT 1 antibodies were further tested in vivo for cancer therapeutic efficacy, especially in combination with immune checkpoint inhibitor therapy. Two cancer models were used, an anti-PD1 -responsive 1956 sarcoma subcutaneous transplantation tumor model that responds completely to an early-onset scheme of anti- PD1 treatment, but not to late-onset schemes (Gubin et al, Nature. 2014 Nov 27; 515(7528): 577-581 ), and polyoma middle T oncoprotein (PyMT-BO1 ) orthotopic breast tumor which are only marginally sensitive to treatment with immune checkpoint inhibitors (Su et al. Cancer Res. 2016 Jun 15; 76(12): 3484-3495). 956 sarcoma tumor cells were injected subcutaneously to the back of the mice (FIG. 12A-12D). PyMT-BO1 tumor cells were injected orthotopically to the mammary fat pad of the female mice (FIG. 12E-12F). Mice were treated with MYCT1 antibody, anti-PD1 antibody, or a combination of MYCT1 antibody and anti-PD1 antibody. anti-PD1 antibody was administered through i.p injection at 250pg/injection/mouse, and 2B4F9D3 or 11 B6 were through i.p injection at administered with 330pg/injection/mouse. Regression of the tumor burden was measured for each condition. Tumors treated with anti-MYCT1 antibodies and anti-PD1 antibodies show significant growth inhibition and/or regression in both the tumor models (FIG. 12A-12G). Representative raw data on tumor volume measurements are provided in Table 9A-9D. These results suggested that anti-MYCT1 antibody synergistically work with anti-PD1 antibodies to reduce tumor burden and indicated that anti-MYCT1 antibody enhanced anti-tumor immunity.

Table 9A: Tumor volume measurements in mm in PBS treated mice

Table 9B: Tumor volume measurements in mm in anti-PD1 treated mice

Table 9C: Tumor volume measurements in mm in 2B4 + Anti-PD1 treated mice

Table 9D: Tumor volume measurements in mm in 11B6 + Anti-PD1 treated mice Summary

[00341] Multiple MYCT1 antibodies was identified, isolated and sequenced including antibody clones 11 B6, 2B4 (subclones 2B4F9D3, 2B4F9D9), 3E3, 8D2, and 9E2. In vivo characterization revealed that these antibodies can reduce angiogenesis related processes including sprouting, tube formation and wound closing in both mouse and human endothelial cells. In vivo studies using tumor model showed that combinatorial treatment of MYCT1 antibodies with anti-PD1 antibodies can reduce tumor burden in both immune checkpoint inhibitor -responsive and -refractory tumors. These results have substantiated that anti-MYCT1 antibodies reduce angiogenesis in tumor cells, improve anti-tumor immunity, and can synergistically reduce tumor burden in combination with immune checkpoint inhibitors.