Abstract
Abstract The use of antigen-specific T cell derived induced iPSCs as a cell source for regeneration of cytotoxic T lymphocytes (CTLs) have advantages in rejuvenation profile, and reproducible number of CTLs. However for the safe and efficient regenerated T cell immunotherapy, strict antigen specificity is essential. Here we report CD8αβ T cells differentiated from T cell-derived iPSCs underwent additional rearrangement of the T cell receptor (TCR) α-chain gene at the CD4/CD8 double positive stage during in vitro differentiation and lost antigen specificity. CRISPR knockout of a recombinase gene in the T-iPSCs successfully prevented this additional TCR rearrangement. Moreover, when CD8αβ T cells were differentiated from non-T cell-derived but antigen-specific TCR-transduced iPSCs, they showed monoclonal expression of the transduced TCR. TCR stabilized regenerated CD8αβ T cells effectively inhibit tumor growth in xenograft cancer models. These approaches could contribute to safe and effective regenerative T cell immunotherapies. Citation Format: Atsutaka Minagawa, Akitsu Hotta, Yohei Kawai, Yutaka Yasui, Yasushi Uemura, Masaki Yasukawa, Tetsuya Nakatsura, Shin Kaneko. T cell receptor-stabilized regenerated CD8ab cytotoxic T lymphocytes for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3585.
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