Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells

• DOI: 10.1038/s41551-022-00969-0
• Publication Date: 2022-12-12T17:06:28Z
• Authors: Tatsuki Ueda; Sara Shiina; Shoichi Iriguchi; Seitaro Terakura; Yohei Kawai; Ryotaro Kabai; Satoko Sakamoto; Akira Watanabe; Kohei Ohara; Bo Wang; Huaigeng Xu; Atsutaka Minagawa; Akitsu Hotta; Knut Woltjen; Yasushi Uemura; Yuzo Kodama; Hiroshi Seno; Tetsuya Nakatsura; Koji Tamada; Shin Kaneko
• Keywords: clone (Java method)

Abstract The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency T cells at tumour site. Here we show that CD8αβ cytotoxic CAR in can be enhanced by deriving expanding them from a single human induced-pluripotent-stem-cell clone bearing selected for efficient differentiation. We also effector further genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling, transducing with genes encoding membrane-bound interleukin-15 (IL-15) its subunit IL-15Rα. In multiple tumour-bearing animal models, engineered hiPSC-derived led to therapeutic outcomes similar those primary CD8 same CAR. optimization derived pluripotent stem may aid development long-lasting antigen-specific treatment tumours.