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Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model.
iScience ( IF 4.447 ) Pub Date : 2020-04-06 , DOI: 10.1016/j.isci.2020.100998
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

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.
更新日期:2020-04-21

 

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