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

Abstract

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.

Journal

• iScience

  iScience 23 (4), 100998-, 2020-04-24

  Elsevier BV

Keywords

• Cancer
• Cellular Therapy
• Immunological Methods

Details

• CRID: 1050003824759588608
• NII Article ID: 120006869553
• NII Article ID: 120006826710
• ISSN: 25890042
• DOI: 10.1016/j.isci.2020.100998
• HANDLE: 2433/250312
• Web Site: https://ousar.lib.okayama-u.ac.jp/58703
• Web Site: https://api.elsevier.com/content/article/PII:S2589004220301826?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S2589004220301826?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN