Cloning and expansion of antigen-specific T cells using iPSC technology: A novel strategy for cancer immunotherapy

Abstract

Cytotoxic T lymphocytes (CTLs) represent the most promising therapeutic avenue in cancer immunotherapy, yet most of the currently ongoing trials utilizing CTLs are still not effective enough to cure patients. To overcome this problem, we came up with the idea to apply induced pluripotent stem cell (iPSC) technology to the cloning and expansion of CTLs. When iPSCs are established from antigen-specific T cells (T-iPSCs), these T-iPSCs should inherit rearranged genomic structures of T cell receptor genes, and thus all T cells regenerated from T-iPSCs should express the same T cell receptor (TCR). Since iPSCs can be expanded almost unlimitedly, it is possible to obtain as many fresh CTLs as needed. Pursuing this idea, we have recently succeeded in regenerating melanoma antigen MART1-specific CTLs from T-iPSCs originally derived from a melanoma patient. Our study illustrates an approach for the cloning and expansion of functional antigen-specific CTLs that might be applicable in cell-based cancer therapy.