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

• Published in: iScience Vol. 23; no. 4; p. 100998
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.04.2020; Elsevier
• Subjects: Cancer; Cellular Therapy; Immunological Methods; Immunological Methods; Cellular Therapy; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.100998

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells 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. [Display omitted] •Patient-derived xenograft of renal cell carcinoma was used in a cell-therapy model•Cytotoxic T lymphocytes (CTLs) that target WT1-antigen were used as effector cells•CTLs produced from iPSCs transduced with WT1-TCR genes showed efficacy in the model•The present results demonstrate the feasibility of our strategy against solid tumors Cellular Therapy; Immunological Methods; Cancer