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Development of methods for elimination of multiple myeloma stem cells targeting constitutively activated integrin beta 7

Research Project

Project/Area Number 17H04207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

Hosen Naoki  大阪大学, 医学系研究科, 教授 (10456923)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords多発性骨髄腫 / インテグリン / 癌
Outline of Final Research Achievements

We searched for molecules that cause constitutive activation of integrin β7 in myeloma cells by screening with CRISPR gRNA library or cDNA derived from myeloma cells, but no candidate molecule was obtained. However, we found that the antigen epitope for the activated integrin β7 was expressed upon induction of endoplasmic reticulum stress, a major feature of myeloma cells, with tunicamycin or thapsigargin. Based on these results, we hypothesized that β7 integrin may have a unique conformation in myeloma that is different from the physiological activated conformation, and started a collaboration with a structural biologist.

Academic Significance and Societal Importance of the Research Achievements

β7インテグリンでは生理的な活性化コンフォーメーションと似て非なる「骨髄腫に特有のコンフォーメーション」が存在する可能性を示唆し、真の意味でがんと正常との間に蛋白質の“形”の違いがあるかもしれないという新しいコンセプトを提示することができた。今後このコンセプトを検証し、正しいことが実証できれば、他の様々ながんにおいて様々な蛋白質のがん特異的なコンフォメーションの存在が同定できる可能性が広がり、新たながん治療の開発に役立つ可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (3 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma2019

    • Author(s)
      Hosen Naoki
    • Journal Title

      Cancers

      Volume: 11 Issue: 12 Pages: 2024-2024

    • DOI

      10.3390/cancers11122024

    • NAID

      130007496853

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] The Activated Conformation of Integrin β7 is a Novel Multiple Myeloma-Specific Target for CAR T-cell Therapy.2020

    • Author(s)
      Naoki Hosen
    • Organizer
      2nd European CAR T cell meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The Activated Conformation of Integrin β7 is a Novel Multiple Myeloma-Specific Target for CAR T-cell Therapy.2019

    • Author(s)
      Naoki Hosen
    • Organizer
      The 24th Congress European Hematology Assocoation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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