Abstract 2550: Generation of CAR-iPS-T cells expressing CD8β

Abstract Chimeric antigen receptor (CAR) is an artificial protein that provides HLA-independent antigen specificity to T cells. CAR-T therapy has shown remarkable clinical responses especially in hematologic malignancies. But this therapy needs cell preparation for each patient. That limits its applicability. We have reported regeneration of T cells from iPSCs (Cell Stem Cell 2013). This technology provides unlimited number of T cells, so CAR-T therapy using iPSCs can broadens its applicability. Regenerated T cells previously described in some reports including ours have some different characters from peripheral T cells. In particular, they express only CD8α, and do not express CD8β. We successfully generate CAR-iPS-T cells expressing CD8β with some modification of differentiation protocols. We assayed the function of CAR-iPS-T cells in view of the difference between CD8β positive and negative iPS-T cells. We found CD8β positive CAR-iPS-T cells showed enhanced function to suppress tumor progression compared with CD8β negative CAR-iPS-T cells in subcutaneous xenograft model. In vivo kinetics study revealed that CD8β positive CAR-iPS-T cells have superior function to traffic to target expressing tumor site and enhanced sustainability in vivo compared with CD8β negative CAR-iPS-T cells. These findings indicate that CD8β positive CAR-iPS-T cells may be a potent cell source for iPSC-based cancer immunotherapy. Citation Format: Tatsuki Ueda, Shoichi Iriguchi, Yohei Kawai, Atsutaka Minagawa, Hiroyuki Miyoshi, Seitaro Terakura, Yasushi Uemura, Knut Woltjen, Yuzo Kodama, Hiroshi Seno, Yasumichi Hitoshi, Tetsuya Nakatsura, Koji Tamada, Shin Kaneko. Generation of CAR-iPS-T cells expressing CD8β [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 2550.