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Development of innovative combined cancer immunotherapy using immune checkpoint blockade for digestive cancers

Research Project

Project/Area Number 19K21359
Project/Area Number (Other) 18H06267 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0906:Surgery related to the biological and sensory functions and related fields
Research InstitutionFukuoka Dental College

Principal Investigator

Okano Shinji  福岡歯科大学, 口腔歯学部, 准教授 (10380429)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌免疫療法 / 免疫チェックポイント阻害剤 / 癌集学的治療 / 癌抗原特異的T細胞 / 癌ゲノム不安定性 / PD-1 / 腫瘍免疫 / T細胞 / 化学療法
Outline of Research at the Start

免疫チェックポイント阻害剤を用いた集学的治療は患者さんの予後の改善に寄与すると考えられるが、免疫チェックポイント阻害剤と現行の集学的治療との交互作用、特に癌組織のみならず腫瘍抗原特異的T細胞への影響に関する基礎的・臨床的知見が不足しており、その解明が緊急的課題となっている。本研究では、マウス消化器癌腫瘍モデル及びヒト消化器癌組織と患者自身の免疫担当細胞を用いて、各癌腫の標準的化学療法とチェックポイント阻害剤併用療法(がん免疫複合療法)の抗腫瘍効果の詳細な分子機序を解明し、併用薬剤の選択法、投与量、時期の基本原理原則を明らかにし、奏功性の高いがん免疫複合療法を開発する基盤を作る。

Outline of Final Research Achievements

It is important to obtain knowledge about interaction between immune checkpoint inhibitors (ICs) and current standard cancer treatments in combined cancer immunotherapy (CCI).We assessed mechanisms of antitumor effects in the CCI and basic principle for the administration timing of combined drugs using mouse colon adenocarcinoma models. The chemotherapy induced immunogenic cancer cell death and tumor-specific cytotoxic T lymphocytes (TC) responses, and dramatically increased numbers of IFN-gamma producing CD4 and CD8 T cells and TC within the tumors, suggesting that the administration order of the chemotherapy followed by the anti-PD-1 antibody was important (anti-PD-1 treatment was essential for in vivo anti-tumor effects by TC).Chemotherapy reduced not only tumor cell numbers, but also numbers of myeloid-derived suppressor cells and TC. Development of drugs to selectively induce cell death of specific target cells is a promising strategy for new CCIs.

Academic Significance and Societal Importance of the Research Achievements

免疫原性癌細胞死から腫瘍抗原特異的T細胞誘導及び抗腫瘍効果に至る「殺細胞治療関連がん免疫サイクル」を考慮に入れた効率の良いがん複合免疫療法の投与レジメ検討の提唱と新規がん免疫複合療法の開発の一つの標的を提案することができ、がん患者の予後改善のために本研究分野の更なる推進と応用が期待されることを示すことができた。

Report

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

    (8 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results)

  • [Journal Article] Non-transmissible MV Vector with Segmented RNA Genome Establishes Different Types of iPSCs from Hematopoietic Cells2020

    • Author(s)
      Hiramoto T、Tahara M、Liao J、Soda Y、Miura Y、Kurita R、Hamana H、Inoue K、Kohara H、Miyamoto S、Hijikata Y、Okano S、Yamaguchi Y、Oda Y、Ichiyanagi K、Toh H、Sasaki H、Kishi H、Ryo A、Muraguchi A、Takeda M、Tani K
    • Journal Title

      Molecular Therapy

      Volume: 28 Issue: 1 Pages: 129-141

    • DOI

      10.1016/j.ymthe.2019.09.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cisplatin-induced programed cell death ligand-2 expression is associated with metastasis ability in oral squamous cell carcinoma2020

    • Author(s)
      Sudo S, Kajiya H, Okano S, Sasaki M, Katsumata Y, Ohno J, Ikebe T, Hiraki A, Okabe K
    • Journal Title

      Cancer Sci

      Volume: 111 Issue: 4 Pages: 1113-1123

    • DOI

      10.1111/cas.14336

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer2019

    • Author(s)
      Imai Daisuke、Yoshizumi Tomoharu、Okano Shinji、Itoh Shinji、Ikegami Toru、Harada Noboru、Aishima Shinichi、Oda Yoshinao、Maehara Yoshihiko
    • Journal Title

      Journal of Surgical Research

      Volume: 240 Pages: 115-123

    • DOI

      10.1016/j.jss.2019.02.038

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 消化器がんにおける免疫チェックポイント阻害剤を用いたがん免疫複合療法の開発2019

    • Author(s)
      岡野 慎士
    • Journal Title

      Medical Science Digest

      Volume: 45 Pages: 720-723

    • Related Report
      2018 Annual Research Report
  • [Presentation] Anti-PD1 treatment is essential for T-cell-dependent anti-tumor effects of FOLFIRI to a MMR-proficient mouse colon cancer2019

    • Author(s)
      岡野慎士、沖英次、佐伯浩司、吉本尚平、工藤健介、木村光一、小田義直、森 正樹、前原喜彦、池田哲夫
    • Organizer
      第108回日本病理学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非MMR欠損大腸癌モデルにおいてFOLFIRI療法によるT細胞依存性抗腫瘍効果発揮に抗PD-1抗体療法は必須である2019

    • Author(s)
      岡野慎士、沖英次、佐伯浩司、吉本尚平、工藤健介、木村光一、小田義直、森 正樹、前原喜彦、池田哲夫
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非MMR欠損大腸癌モデルにおいてFOLFIRI療法によるT細胞依存性抗腫瘍効果発揮に抗PD-1抗体療法は必須である2019

    • Author(s)
      岡野慎士、沖英次、小田義直、森 正樹、前原喜彦、池田哲夫
    • Organizer
      第24回日本外科病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Anti-programmed cell death 1 antibody enhances anti-tumor effect of chemotherapy with folinic acid, fluorouracil and irinotecan in a preclinical murine model of colon cancer2018

    • Author(s)
      岡野慎士、沖英次、 中司 悠、佐伯浩司、 安藤幸滋、中島雄一郎、小田義直、吉本尚平、 工藤健介、木村光一、前原喜彦、池田哲夫
    • Organizer
      第29回日本消化器癌発生学会学術総会
    • Related Report
      2018 Annual Research Report

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Published: 2018-08-27   Modified: 2024-03-26  

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