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

Autor: 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
Rok vydání: 2022
Předmět:
Zdroj: Nature Biomedical Engineering. 7:24-37
ISSN: 2157-846X
Popis: The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency of T cells at the tumour site. Here we show that the proliferation of CD8αβ cytotoxic CAR T cells in solid tumours can be enhanced by deriving and expanding them from a single human induced-pluripotent-stem-cell clone bearing a CAR selected for efficient differentiation. We also show that the proliferation and persistency of the effector cells in the tumours can be further enhanced by genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling, and by transducing the cells with genes encoding for membrane-bound interleukin-15 (IL-15) and its receptor subunit IL-15Rα. In multiple tumour-bearing animal models, the engineered hiPSC-derived CAR T cells led to therapeutic outcomes similar to those of primary CD8 T cells bearing the same CAR. The optimization of effector CAR T cells derived from pluripotent stem cells may aid the development of long-lasting antigen-specific T-cell immunotherapies for the treatment of solid tumours.
CARシグナルを補完する遺伝子改変により *iCAR-T細胞の固形がん治療効果が改善される. 京都大学プレスリリース. 2022-12-13.
Genetic modifications boosting CAR signaling improve the therapeutic efficacy of iPSC-derived CAR-T cells against solid tumors. 京都大学プレスリリース. 2022-12-13.
Databáze: OpenAIRE
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