Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model

Kashima, Soki, Maeda, Takuya, Masuda, Kyoko, Nagano, Seiji, Inoue, Takamitsu, Takeda, Masashi, Kono, Yuka, Kobayashi, Takashi, Saito, Shigeyoshi, Higuchi, Takahiro, Ichise, Hiroshi, Kobayashi, Yuka, Iwaisako, Keiko, Terada, Koji, Agata, Yasutoshi, Numakura, Kazuyuki, Saito, Mitsuru, Narita, Shintaro, Yasukawa, Masaki, Ogawa, Osamu, Habuchi, Tomonori, Kawamoto, Hiroshi

doi:10.1016/j.isci.2020.100998

Current adoptive Tcell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's Tcells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from Tcells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors.

Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model

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