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Development of novel CAR-T cell therapy for multiple myeloma

Research Project

Project/Area Number 18K08330
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionInternational University of Health and Welfare (2019-2020)
Ehime University (2018)

Principal Investigator

Asai Hiroaki  国際医療福祉大学, 国際医療福祉大学三田病院, 准教授 (00726838)

Co-Investigator(Kenkyū-buntansha) 安川 正貴  愛媛大学, プロテオサイエンスセンター, 教授 (60127917)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords遺伝子改変T細胞療法 / CAR-T / NY-ESO-1 / 多発性骨髄腫 / 細胞免疫療法
Outline of Final Research Achievements

NY-ESO-1 is an immunogenic cancer-testis antigen reported to express in approximately 60% of advanced myelomas, and correlated to tumor proliferation and high-risk features. Here, we have generated CAR possessing the single chain fragment variable (scFv) specific for the HLA-A2/NY-ESO-1_157-165 complex (A2/NY-ESO-1_157). Using HLA-A2+NY-ESO-1+ myeloma cells and peptides presented by HLA-A2 molecules as a model, these redirected CAR-T cells recognized and killed HLA-A2+NY-ESO-1+ myeloma cells in an A2/NY-ESO-1_157-specific manner in vitro. Moreover, CAR-activated T cells showed sufficient functional avidity, as assessed by cytokine production and killing activity, and displaying antitumor reactivity against HLA-A2+NY-ESO-1+ myeloma cells in vivo. Thus, our experimental findings strongly support the continued development of NY-ESO-1-TCR engineered T cells for treatment of myeloma.

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫に対する新規治療法が開発されているが、未だ治癒に結びつける治療法は確立されていない。本研究は、本来T細胞がTCRを介して認識するがん抗原ペプチドとHLA複合体を抗体で認識させるという極めてがん特異性に富んだ治療法である。類似の研究はこれまでWT1-HLA-A2複合体に対するCAR-T開発が米国で行われているのみである。本研究のような抗原特異的細胞免疫療法は難治性造血器腫瘍である多発性骨髄腫に対する治癒を目指せる新規治療法となり得ることが大いに期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Direct comparisoin of target-reactivity and cross-reactivity induced by CAR-and BiTE-redirected T cells for the development of antibody-based T-cell therapy.2019

    • Author(s)
      Masaki Maruta, Toshiki Ochi, Kazushi Tanimoto, Hiroaki Asai, et al.
    • Journal Title

      Scientific reports

      Volume: 9 Issue: 1 Pages: 13293-13293

    • DOI

      10.1038/s41598-019-49834-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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