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

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.

iScience. 2020 Apr 06 [Epub ahead of print]

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

Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Urology, Akita University Graduate School of Medicine, Akita, Japan; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan., Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan., Department of Urology, Akita University Graduate School of Medicine, Akita, Japan., Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan., Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan., Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University, Osaka, Japan., Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Osaka, Japan., Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan., Department of Biochemistry and Molecular Biology, Shiga University of Medical School, Shiga, Japan., Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Matsuyama, Ehime, Japan., Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: .

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