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Metabolic Reprogramming Requires Stem Cell Memory T Cell phenotypes for Cancer Immunotherapy

Research Project

Project/Area Number 18K15290
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionKeio University

Principal Investigator

KONDO TAISUKE  慶應義塾大学, 医学部(信濃町), 助教 (60803765)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsがん免疫 / 代謝 / 免疫記憶 / ミトコンドリア / CAR-T療法 / がん免疫療法 / 免疫代謝 / 白血病 / 腫瘍免疫 / 細胞移入療法 / 腫瘍免疫学 / 代謝制御
Outline of Final Research Achievements

Stem cell memory T (TSCM) cells are well-known as one of less differentiated-memory T cell population. We previously established a method for the induction of TSCM-like cells in vitro. With the support of the grant, we applied the established method for chimeric antigen receptor engineered-T (CAR-T) cell therapy and succeeded to convert normal CAR-T cells into TSCM-like CAR-T cells. The TSCM-like CAR-T cells showed potent anti-tumor activity in humanized leukemia model. We also found that the enhanced anti-tumor activity was dependent on mitochondrial biogenesis. The study has already been published on Cancer Research journal on 2020.

Academic Significance and Societal Importance of the Research Achievements

キメラ型抗原受容体発現T(CAR-T)細胞移入療法はチェックポイント阻害剤と並ぶ、新たながん免疫療法である。米国ではすでに製剤として認可されており、小児および若年白血病患者に対して、高い治療成績を示している。しかしながら、長期間の寛解維持が困難であり、その原因の一つとして移入する細胞の品質が問題となっていた。本研究は従来のCAR-T細胞をより長期間体内で維持される様に改善する方法であり、新しいがん治療法として期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.2020

    • Author(s)
      Kondo T, Ando M, Nagai N, Tomisato W, Srirat T, Liu B, Mise-Omata S, Ikeda M, Chikuma S, Nishimasu H, Nureki O, Ohmura M, Hayakawa N, Hishiki T, Uchibori R, Ozawa K, Yoshimura A
    • Journal Title

      Cancer Res

      Volume: 80 Issue: 3 Pages: 471-483

    • DOI

      10.1158/0008-5472.can-19-1196

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy.2018

    • Author(s)
      Taisuke Kondo Yuki Imura Shunsuke Chikuma Sana Hibino Setsuko Omata‐Mise Makoto Ando Takashi Akanuma Mana Iizuka Ryota Sakai Rimpei Morita Akihiko Yoshimura
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 7 Pages: 2130-2140

    • DOI

      10.1111/cas.13648

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Metabolic Reprogramming requires Stem Cell Memory T Cells phenotypes for Adoptive Immunotherapy2018

    • Author(s)
      近藤泰介
    • Organizer
      日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ミトコンドリア制御によるステムセルメモリーT細胞の誘導と細胞移入療法への応用2018

    • Author(s)
      近藤泰介
    • Organizer
      日本がん免疫学会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] CD45RA+およびCCR7+の細胞表面マーカーを有するT細胞の製造方法2019

    • Inventor(s)
      近藤泰介、吉村昭彦、慶應義塾大学、第一三共
    • Industrial Property Rights Holder
      慶應義塾大学、第一三共
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-195206
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2021-02-19  

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