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Kashima, Soki Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Maeda, Takuya Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Masuda, Kyoko Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Nagano, Seiji Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Inoue, Takamitsu Department of Urology, Akita University Graduate School of Medicine
Takeda, Masashi Department of Urology, Kyoto University Graduate School of Medicine
Kono, Yuka Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Kobayashi, Takashi Department of Urology, Kyoto University Graduate School of Medicine
Saito, Shigeyoshi Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University
Higuchi, Takahiro Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine ORCID Kaken ID publons researchmap
Ichise, Hiroshi Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Kobayashi, Yuka Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Iwaisako, Keiko Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University
Terada, Koji Department of Biochemistry and Molecular Biology, Shiga University of Medical School
Agata, Yasutoshi Department of Biochemistry and Molecular Biology, Shiga University of Medical School
Numakura, Kazuyuki Department of Urology, Akita University Graduate School of Medicine
Saito, Mitsuru Department of Urology, Akita University Graduate School of Medicine
Narita, Shintaro Department of Urology, Akita University Graduate School of Medicine
Yasukawa, Masaki Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University
Ogawa, Osamu Department of Urology, Kyoto University Graduate School of Medicine
Habuchi, Tomonori Department of Urology, Akita University Graduate School of Medicine
Kawamoto, Hiroshi Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
Abstract
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.
Keywords
Cancer
Cellular Therapy
Immunological Methods
Published Date
2020-04-24
Publication Title
iScience
Volume
volume23
Issue
issue4
Publisher
Cell Press
Start Page
100998
ISSN
25890042
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2020 The Author(s).
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PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1016/j.isci.2020.100998
License
http://creativecommons.org/licenses/by/4.0/
Citation
Kashima S, Maeda T, Masuda K, et al. Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model. iScience. 2020;23(4):100998. doi:10.1016/j.isci.2020.100998
Funder Name
Japan Society for the Promotion of Science
助成番号
18J10676
Open Access (Publisher)
OA
Open Archive (publisher)
Non-OpenArchive