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US 12,668,777 B2Granted
Chimeric antigen receptor T cells and methods of use thereof
AssigneeAugusta University Research Institute, Inc.
InventorGang Zhou
Life of this patent
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Abstract
Disclosed herein are engineered polyfunctional CD4+ T cells/CAR T cells and methods of their use for the treatment of cancers. One embodiment provides a method of producing polyfunctional CD4+ T cells by constitutively activating STAT5A in the cells to induce a polyfunctional phenotype. Also provided is a method of reversing exhaustion in tumor-specific CD4+ T cells by engineering the cells to express Fos, Jun, Nr4a1, or combinations thereof but not express Tox, Pdcd1, Ctla4, Haver2, Lag3, Tigit, Slam6, Nrf4a2, and administering the engineered cells to a subject.
Claims6
A method of adoptive transfer comprising:
- a) isolating CD4+ and CD8+ T cells from a subject,
- b) expanding the CD4+ and CD8+ T cells ex vivo,
- c) genetically engineering the CD4+ and CD8+ T cells to produce polyfunctional CD4+ and CD8+ T cells which express a cluster of differentiation 19 protein chimeric antigen receptor (CD 19CAR) and constitutively express signal transducer and activator of transcription 5 (Stat5a) by transducing the CD4+ and CD8+ T cells with SEQ ID NO:
- 1 or 2, and
- d) administering the polyfunctional CD4+ and CD8+ T cells expressing CD19CAR and constitutively expressing Stat5a to the subject in an amount effective to induce an immune response to cancer,
- wherein the subject has a hematological cancer,
- wherein the polyfunctional CD4+ and CD8+ T cells expressing CD19CAR reverse exhaustion in tumor-specific CD4+ and CD8+ T cells and the constitutive STAT5a activity induces epigenetic changes and changes in expression in comparison to control CD4+ and CD8+ T cells in hematological cancer, and
- wherein the polyfunctional CD4+ and CD8+ T cells expressing CD19CAR and constitutively expressing Stat5a, when administered in combination, synergistically enhances tumor infiltration and retention of CD4+ and CD8+ T cells compared to control CD4+ and CD8+ T cells in hematological cancer.
5 more elements
Dependencies are inferred from the claim text.