Development of fail-safe system for human iPSC-derived tumor by CAR-T cell therapyCAR-T cell therapy
Project/Area Number |
20K21608
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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Research Institution | Keio University |
Principal Investigator |
Fukuda Keiichi 慶應義塾大学, 医学部(信濃町), 教授 (20199227)
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Co-Investigator(Kenkyū-buntansha) |
岡田 麻里奈 慶應義塾大学, 医学部(信濃町), 助教 (00594582)
谷口 智憲 慶應義塾大学, 医学部(信濃町), 講師 (40424163)
遠山 周吾 慶應義塾大学, 医学部(信濃町), 講師 (90528192)
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Project Period (FY) |
2020-07-30 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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Keywords | CART細胞療法 / 未分化細胞除去法 / iPS細胞 / 心筋細胞移植 / CAR-T細胞療法 / 奇形種形成抑制 / 奇形腫形成抑制 / ヒト多能性幹細胞 / 再生医療 / CAR-T細胞 / 腫瘍化 / 心筋細胞 |
Outline of Research at the Start |
本研究ではGPC3を標的としたCAR-T細胞療法により“再生医療における低侵襲的腫瘍除去法を確立する”というこれまでに例のない画期的手法を開発することを目指す。具体的には、ヒトiPS細胞由来腫瘍に特異的に発現する抗原を認識するCAR-T細胞を樹立し、in vitroおよびin vivoにおける腫瘍化細胞除去効果および腫瘍退縮効果を評価する予定である。
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Outline of Final Research Achievements |
We completed the production of monoclonal antibody against GPC3, the production of chimeric antigen receptor (CAR) by gene modification, and the production of CAR-T against GPC3, and confirmed the strong cytotoxic effect on GPC3-expressing cells. Furthermore, we confirmed that it did not act on differentiated cells from iPS cells, but only on residual iPS cells. In animal experiments with mice, we elucidated that CAR-T cells administration suppressed teratoma formation when iPS cells were transplanted.
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Academic Significance and Societal Importance of the Research Achievements |
申請者らはこれまでに、ヒトiPS細胞に特異的に発現し、分化心筋細胞には発現していない細胞膜表面抗原としてGPC3を同定し、これを標的抗原とするGPC3特異的細胞傷害性T細胞 (CTL) 療法を開発してきた(BBRC 2019)。また、ヒトiPS細胞由来の奇形腫においてGPC3が高発現していることを初めて見出し、GPC3を標的としたCAR-T細胞療法の免疫学的アプローチにより再生医療における全ての領域で応用可能な非侵襲的腫瘍除去法の確立を可能とした。
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Adoptive cell therapy using tumor-infiltrating lymphocytes for melanoma refractory to immune-checkpoint inhibitors.2021
Author(s)
Hirai I, Funakoshi T, Kamijuku H, Fukuda K, Mori M, Sakurai M, Koda Y, Kato J, Mori T, Watanabe N, Noji S, Yaguchi T, Iwata T, Ohta S, Fujita T, Tanosaki R, Handa M, Okamoto S, Amagai M, Kawakami Y.
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Journal Title
Cancer Sci.
Volume: 112
Issue: 8
Pages: 3163-3172
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells2021
Author(s)
Shota Someya, Shugo Tohyama, Kotaro Kameda, Sho Tanosaki, Yuika Morita, Kazunori Sasaki, Moon Il Kang, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Tomohiko Umei, Otoya Sekine, Taijun Moriwaki, Hideaki Kanazawa, Eiji Kobayashi, Jun Fujita, Keiichi Fukuda
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Journal Title
iScience
Volume: 24
Issue: 2
Pages: 102090-102090
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells2020
Author(s)
Sho Tanosaki, Shugo Tohyama, Jun Fujita, Hiroki Nakanishi, Takayo Ohto-Nakanishi, Tomohiko Akiyama, Yuika Morita, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Hideaki Kanazawa, Masahiro Sugimoto, Minoru S.H. Ko, Makoto Suematsu, Keiichi Fukuda
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Journal Title
iScience
Volume: 23
Issue: 9
Pages: 101535-101535
DOI
Related Report
Peer Reviewed / Open Access
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