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Development of immunotherapy for glioblastoma using EGFRvIII specific CAR transduced immune cells

Research Project

Project/Area Number 16K10767
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionNara Medical University

Principal Investigator

Nishimura Fumihiko  奈良県立医科大学, 医学部, 講師 (70433331)

Co-Investigator(Kenkyū-buntansha) 中村 光利  奈良県立医科大学, 医学部附属病院, 研究員 (00305715)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords悪性神経膠芽腫 / キメラ受容体 / ナチュラルキラー細胞 / EGFRvIII / アポトーシス / Glioblastoma / Immunotherapy / Chimeric antigen / Natural killer cell / T cell / 脳腫瘍学 / 腫瘍免疫
Outline of Final Research Achievements

Among glioblastoma cells, 40% of tumor cells express EGFRvIII antigen. Using tumor growth inhibition assay, we have proved EGFRvIII tumor antigen specific chimeric antigen receptor(CAR)-natural killer(NK)cells(KHYG-1) have an ability to inhibit the tumor growth of U87 tumor cell line which expressed EGFRvIII antigen. Also, using apoptosis detection assay, we have proved that EGFRvIII-CAR-NK-KHYG-1 induced tumor antigen specific apoptosis against U87. We reported those results on ANTICANCER RESEARCH 38:5049-5056(2018).

Academic Significance and Societal Importance of the Research Achievements

悪性神経膠芽腫に対する治療の3本柱は、手術、化学療法、放射線治療であるが、それでも難治性の腫瘍であるため、治療が非常に有効な可能性のある免疫療法が必要である。我々は、免疫細胞であるナチュラルキラー細胞株に、遺伝子導入を用いて、腫瘍抗原特異的なキメラ受容体を導入し、腫瘍増殖抑制効果と、腫瘍抗原特異的なアポトーシスが誘導されることを証明した。この基礎研究により、将来的に臨床応用の可能性も考えられ、学術的にも社会的にも意義があると考えられる。今後は、さらに動物実験などでのキメラ受容体発現ナチュラルキラー細胞の抗腫瘍効果を評価していきたいと考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells.2018

    • Author(s)
      Murakami T, Nakazawa T(equally contribution), Natsume A, Nishimura F, Nakamura M, Matsuda R, Omoto K, Tanaka Y, Shida Y, Park YS, Motoyama Y, Nakagawa I, Yamada S, Tamura K, Takeshima Y, Takamura Y,
    • Journal Title

      Anticancer Res

      Volume: 38 Issue: 9 Pages: 5049-5056

    • DOI

      10.21873/anticanres.12824

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Establishment of an efficient ex-vivo expansion method for highly purified human natural killer cells and evaluation of their antitumor activity on glioblastoma2019

    • Author(s)
      Nakazawa T, Tanaka Y, Shida Y, Nakamura M, Nishimura F, Matsuda R, Murakami T, Nakagawa I, Motoyama Y, Tsujimura T, Nakase H.
    • Organizer
      Keystone Symposia: Innate and Non-Classical Immune Cells in Cancer Immunotherapy
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells2019

    • Author(s)
      Murakami T, Nakazawa T, Nishimura F, Natsume A, Wakabayashi T, Nakase H
    • Organizer
      European Association for Cancer Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel human NK cell line carrying CAR targeting EGFRvIII induces antitumor effects in glioblastoma cells in vitro2018

    • Author(s)
      村上敏春、中澤務、夏目敦至、西村文彦、中村光利、松田良介、至田洋一、若林俊彦、中瀬裕之
    • Organizer
      第19回日本分子脳神経外科学会
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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