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

Maria Themeli, Christopher C. Kloss, Giovanni Ciriello, Victor D. Fedorov, Fabiana Perna, Mithat Gonen, Michel Sadelain*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Progress in adoptive T-cell therapy for cancer and infectious diseases 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. Here we combine induced pluripotent stem cell (iPSC) and chimeric antigen receptor (CAR) 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.

Original languageEnglish
Pages (from-to)928-933
Number of pages6
JournalNature Biotechnology
Volume31
Issue number10
DOIs
Publication statusPublished - Oct 2013

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