Title:
PRE-EFFECTOR CAR-T CELL GENE SIGNATURES
Document Type and Number:
WIPO Patent Application WO/2023/081894
Kind Code:
A3
Abstract:
The present disclosure relates generally to methods for generating a pre-effector gene signature for determining the cytotoxic effector potential of a preparation of chimeric antigen receptor (CAR) T cells comprising measuring single-cell gene expression data and endogenous T cell receptor (TCR) sequencing data of the preparation of CAR T cells. The present invention relates also to methods for determining the cytotoxic effector potential of a preparation of CAR T cells or a subset of CAR T cells therefrom as well as methods for treating a cancer in a subject in need thereof by administering a preparation of CAR T cells determined to have a cytotoxic effector potential.
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Inventors:
THOMAS PAUL (US)
GOTTSCHALK STEPHEN (US)
WILSON TAYLOR (US)
CRAWFORD JEREMY (US)
KIM HYUNJIN (US)
GOTTSCHALK STEPHEN (US)
WILSON TAYLOR (US)
CRAWFORD JEREMY (US)
KIM HYUNJIN (US)
Application Number:
PCT/US2022/079410
Publication Date:
June 08, 2023
Filing Date:
November 07, 2022
Export Citation:
Assignee:
ST JUDE CHILDRENS RES HOSPITAL INC (US)
International Classes:
G06N20/00; C12Q1/6809
Domestic Patent References:
| WO2019051335A1 | 2019-03-14 | |||
| WO2020047452A2 | 2020-03-05 | |||
| WO2020092455A2 | 2020-05-07 |
Other References:
SHEIH ALYSSA ET AL: "Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy", NATURE COMMUNICATIONS, vol. 11, no. 1, 10 January 2020 (2020-01-10), XP093014058, Retrieved from the Internet DOI: 10.1038/s41467-019-13880-1
ZHAO XINLEI ET AL: "Evaluation of single-cell classifiers for single-cell RNA sequencing data sets", BRIEFINGS IN BIOINFORMATICS, vol. 21, no. 5, 25 September 2020 (2020-09-25), GB, pages 1581 - 1595, XP055957274, ISSN: 1467-5463, Retrieved from the Internet DOI: 10.1093/bib/bbz096
JOSEPH A. FRAIETTA ET AL: "Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia", NATURE MEDICINE, vol. 24, no. 5, 30 April 2018 (2018-04-30), New York, pages 563 - 571, XP055542305, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0010-1
BEIDER K. ET AL: "IN VITRO ANALYSIS PREDICTS CLINICAL RESPONSE OF B CELL LYMPHATIC MALIGNANCIES TO CD19 CAR-T CELLS: PHENOTYPIC, TRANSCRIPTIONAL AND FUNCTIONAL STUDY", HEMATOLOGICAL ONCOLOGY, vol. 39, no. S2, 1 June 2021 (2021-06-01), US, XP093025457, ISSN: 0278-0232, Retrieved from the Internet DOI: 10.1002/hon.191_2880
MELENHORST J. JOSEPH ET AL: "Decade-long remissions of leukemia sustained by the persistence of activated CD4 + CAR T-cells", BIORXIV, 7 May 2021 (2021-05-07), XP093025448, Retrieved from the Internet [retrieved on 20230220], DOI: 10.1101/2021.05.07.443194
WANG XIAONAN ET AL: "Single-cell transcriptome analysis of CAR T-cell products reveals subpopulations, stimulation, and exhaustion signatures", ONCOIMMUNOLOGY, vol. 10, no. 1, 1 January 2021 (2021-01-01), XP093014055, Retrieved from the Internet DOI: 10.1080/2162402X.2020.1866287
DENG QING ET AL: "Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas", NATURE MEDICINE, vol. 26, no. 12, December 2020 (2020-12-01), pages 1878 - 1887, XP037312832, ISSN: 1078-8956, DOI: 10.1038/S41591-020-1061-7
SHEIH ALYSSA ET AL: "Clonal Kinetics and Single Cell Transcriptional Profiling of Adoptively Transferred CD19 CAR-T Cells", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 132, 29 November 2018 (2018-11-29), pages 702, XP086592726, ISSN: 0006-4971, DOI: 10.1182/BLOOD-2018-99-111350
ZHAO XINLEI ET AL: "Evaluation of single-cell classifiers for single-cell RNA sequencing data sets", BRIEFINGS IN BIOINFORMATICS, vol. 21, no. 5, 25 September 2020 (2020-09-25), GB, pages 1581 - 1595, XP055957274, ISSN: 1467-5463, Retrieved from the Internet
JOSEPH A. FRAIETTA ET AL: "Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia", NATURE MEDICINE, vol. 24, no. 5, 30 April 2018 (2018-04-30), New York, pages 563 - 571, XP055542305, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0010-1
BEIDER K. ET AL: "IN VITRO ANALYSIS PREDICTS CLINICAL RESPONSE OF B CELL LYMPHATIC MALIGNANCIES TO CD19 CAR-T CELLS: PHENOTYPIC, TRANSCRIPTIONAL AND FUNCTIONAL STUDY", HEMATOLOGICAL ONCOLOGY, vol. 39, no. S2, 1 June 2021 (2021-06-01), US, XP093025457, ISSN: 0278-0232, Retrieved from the Internet
MELENHORST J. JOSEPH ET AL: "Decade-long remissions of leukemia sustained by the persistence of activated CD4 + CAR T-cells", BIORXIV, 7 May 2021 (2021-05-07), XP093025448, Retrieved from the Internet
WANG XIAONAN ET AL: "Single-cell transcriptome analysis of CAR T-cell products reveals subpopulations, stimulation, and exhaustion signatures", ONCOIMMUNOLOGY, vol. 10, no. 1, 1 January 2021 (2021-01-01), XP093014055, Retrieved from the Internet
DENG QING ET AL: "Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas", NATURE MEDICINE, vol. 26, no. 12, December 2020 (2020-12-01), pages 1878 - 1887, XP037312832, ISSN: 1078-8956, DOI: 10.1038/S41591-020-1061-7
SHEIH ALYSSA ET AL: "Clonal Kinetics and Single Cell Transcriptional Profiling of Adoptively Transferred CD19 CAR-T Cells", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 132, 29 November 2018 (2018-11-29), pages 702, XP086592726, ISSN: 0006-4971, DOI: 10.1182/BLOOD-2018-99-111350
Attorney, Agent or Firm:
BIRMPAS, Charalampos et al. (US)
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