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

2013; Nature Portfolio; Volume: 31; Issue: 10 Linguagem: Inglês

10.1038/nbt.2678

1546-1696

Maria Themeli, Christopher C. Kloss, Giovanni Ciriello, V D Fedorov, Fabiana Perna, Mithat Gönen, Michel Sadelain,

Virus-based gene therapy research

T cells generated from human iPSCs engineered to express a chimeric antigen receptor display innate lymphoid properties and inhibit tumor growth in mice. Progress in adoptive T-cell therapy for cancer and infectious diseases1,2 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 uncertain3,4,5,6. 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 γδ T cells. Similar to CAR-transduced, peripheral blood γδ 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.