Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy

Progress in adoptive T-cell therapy for cancer and infectious diseases(1,2) is hampered by the lack of readily available, antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an unlimited source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain(3-6). Here we combine induced pluripotent stem cell (iPSC)(7) and chimeric antigen receptor (CAR)(8) technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture. These iPSC-derived, CAR-expressing T cells display a phenotype resembling that of innate gamma delta T cells. Similar to CAR-transduced, peripheral blood gamma delta T cells, the iPSC-derived T cells potently inhibit tumor growth in a xenograft model. This approach of generating therapeutic human T cells 'in the dish' may be useful for cancer immunotherapy and other medical applications.