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Cell Stem Cell. 2013 Jan 3;12(1):31-6. doi: 10.1016/j.stem.2012.12.006.

Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells.

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Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.


Antigen-specific T cells represent a potential therapeutic avenue for a variety of conditions, but current approaches for generating such cells for therapeutic purposes are limited. In this study, we established iPSCs from mature cytotoxic T cells specific for the melanoma epitope MART-1. When cocultured with OP9/DLL1 cells, these iPSCs efficiently generated TCRβ(+)CD4(+)CD8(+) double positive (DP) cells expressing a T cell receptor (TCR) specific for the MART-1 epitope. Stimulation of these DP cells with anti-CD3 antibody generated a large number of CD8(+) T cells, and more than 90% of the resulting cells were specific for the original MART-1 epitope. Stimulation of the CD8(+) T cells with MART-1 antigen-presenting cells led to the secretion of IFNγ, demonstrating their specific reactivity. The present study therefore illustrates an approach for cloning and expanding functional antigen-specific CD8(+) T cells that might be applicable in cell-based therapy of cancer.

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