Cell Press Acta Medica Okayama 25890042 23 4 2020 Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model 100998 EN Soki Kashima Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Takuya Maeda Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Kyoko Masuda Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Seiji Nagano Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Takamitsu Inoue Department of Urology, Akita University Graduate School of Medicine Masashi Takeda Department of Urology, Kyoto University Graduate School of Medicine Yuka Kono Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Takashi Kobayashi Department of Urology, Kyoto University Graduate School of Medicine Shigeyoshi Saito Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University Takahiro Higuchi Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Ichise Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Yuka Kobayashi Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University Keiko Iwaisako Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University Koji Terada Department of Biochemistry and Molecular Biology, Shiga University of Medical School Yasutoshi Agata Department of Biochemistry and Molecular Biology, Shiga University of Medical School Kazuyuki Numakura Department of Urology, Akita University Graduate School of Medicine Mitsuru Saito Department of Urology, Akita University Graduate School of Medicine Shintaro Narita Department of Urology, Akita University Graduate School of Medicine Masaki Yasukawa Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University Osamu Ogawa Department of Urology, Kyoto University Graduate School of Medicine Tomonori Habuchi Department of Urology, Akita University Graduate School of Medicine Hiroshi Kawamoto Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University 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 ƒ¿/ƒÀ 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. No potential conflict of interest relevant to this article was reported.