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Development of new treatments for refractory cancer by combining radiation and immune checkpoint inhibitors

Research Project

Project/Area Number 18H02767
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionOsaka University

Principal Investigator

OGAWA KAZUHIKO  大阪大学, 医学系研究科, 教授 (40253984)

Co-Investigator(Kenkyū-buntansha) 瀬尾 雄二  大阪大学, 医学系研究科, 寄附講座准教授 (00302000)
高橋 豊  大阪大学, 医学系研究科, 助教 (40353461)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords放射線治療 / 免疫治療 / 遠隔転移 / 治療効果 / 免疫療法 / 免疫チェックポイント阻害剤 / 難治性がん / 新規治療法
Outline of Final Research Achievements

By comparing the untreated group, the drug alone group, the radiation (X-ray) alone group, and the drug + radiation combination group in a mouse model of osteosarcoma, the combination of X-ray and PD-L1 antibody and CTLA-4 antibody causes osteosarcoma. It was clarified that a remarkable local and distant antitumor effect can be obtained. It was also clarified that the combined use of carbon beam and PD-L1 antibody and CTLA-4 antibody has a remarkable local and distant antitumor effect on osteosarcoma. Furthermore, it was clarified that the combined use of X-ray, PD-L1 antibody and CTLA-4 antibody in a mouse model of pancreatic cancer has a remarkable local and distant antitumor effect on osteosarcoma.

Academic Significance and Societal Importance of the Research Achievements

放射線治療は癌治療における効果的な局所治療法であるが、近年、免疫チェックポイント阻害剤を併用することにより局所のみならず遠隔転移を有する症例に対しても画期的な効果を上げる可能性があることが分かってきた。
本研究では、骨肉腫を中心とした難治性がんに対する放射線治療と免疫チェックポイント阻害剤の併用治療による局所及び遠隔における治療効果を検討し、局所のみならず、遠隔転移に対しても治療効果が増強することを明らかにした。本研究の成果は、従来局所治療として位置づけられてきた放射線治療を、がんの遠隔転移をも制御できる革新的治療へと発展させる可能性がある。

Report

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

    (5 results)

All 2021 2020 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Local hyperthermia combined with CTLA-4 blockade induces both local and abscopal effects in a murine breast cancer model2021

    • Author(s)
      Ibuki Y, Takahashi Y, Tamari K, Minami K, Seo Y, Isohashi F, Koizumi M, Ogawa K.
    • Journal Title

      Int J Hyperthermia

      Volume: 38 Issue: 1 Pages: 363-371

    • DOI

      10.1080/02656736.2021.1875059

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Radiation Dose Escalation Is Crucial in Anti-CTLA-4 Antibody Therapy to Enhance Local and Distant Antitumor Effect in Murine Osteosarcoma.2020

    • Author(s)
      Takenaka W, Takahashi Y, Tamari K, Minami K, Katsuki S, Seo Y, Isohashi F, Koizumi M, Ogawa K.
    • Journal Title

      Cancers

      Volume: 12(6) Issue: 6 Pages: 1546-1546

    • DOI

      10.3390/cancers12061546

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Carbon ion irradiation enhances the antitumor efficacy of dual immune checkpoint blockade therapy both for local and distant sites in murine osteosarcoma2018

    • Author(s)
      Takahashi Yutaka、Yasui Tomohiro、Minami Kazumasa、Tamari Keisuke、Hayashi Kazuhiko、Otani Keisuke、Seo Yuji、Isohashi Fumiaki、Koizumi Masahiko、Ogawa Kazuhiko
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 6 Pages: 9364-9378

    • DOI

      10.18632/oncotarget.26551

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation enhanced the local and distant anti-tumor efficacy in dual immune checkpoint blockade therapy in osteosarcoma2017

    • Author(s)
      Takahashi Yutaka、Yasui Tomohiro、Tamari Keisuke、Minami Kazumasa、Otani Keisuke、Isohashi Fumiaki、Seo Yuji、Kambe Ryosuke、Koizumi Masahiko、Ogawa Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 12 Pages: e0189697-e0189697

    • DOI

      10.1371/journal.pone.0189697

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Current status of carbon ion radiotherapyCurrent status of carbon ion radiotherapy2018

    • Author(s)
      小川 和彦, 鈴木 修, 八木 雅史, 高橋 豊, 猪股 雅史
    • Organizer
      日本癌学会
    • Related Report
      2018 Annual Research Report

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

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