T cell compositions and methods of use

Claims

This disclosure provides genetically modified iPSC-derived γδT cells and their precursors. It provides a double genomic alteration in the cytokine signaling suppressor 1 (SOCS1) gene and the cytokine-inducible sh2-containing protein (CISH) gene; a triple genomic alteration in genes for SOCS1, CISH, and Bcl-2 interaction mediator in cell death (BIM); a quadruple genomic alteration in genes for SOCS1, CISH, BIM, and cell surface death receptor (FAS); a quintuple genomic alteration in genes for SOCS1, CISH, BIM, β-2-microglobulin (B2M), and class II transactivator (CIITA); and a sextuple genomic alteration in genes for SOCS1, CISH, BIM, B2M, CIITA, and FAS. Genetically modified iPSC-derived γδT cells and their precursors with enhanced tumor proliferation and destruction activity are also provided.Genetically modified iPSC-derived γδT cells and their precursors, which also include CD19 CARs, are provided. This disclosure further provides methods for manufacturing and using such cells, as well as gene-editing systems.