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Elucidation of the mechanism which determines the difference in the therapeutic efficacy of TLR3-specific adjuvant among different tumors

Research Project

Project/Area Number 17H06484
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Tumor therapeutics
Research InstitutionObihiro University of Agriculture and Veterinary Medicine (2018)
Hokkaido University (2017)

Principal Investigator

Takeda Yohei  帯広畜産大学, グローバルアグロメディシン研究センター, 特任助教 (30804447)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords抗腫瘍アジュバント / TLR3アゴニスト / 抗PD-L1抗体療法 / 抗腫瘍免疫 / 抗腫瘍免疫療法 / Toll-like receptor 3 / アジュバント / 細胞傷害性T細胞 / 樹状細胞 / クロスプレゼンテーション / PD-L1発現 / 癌 / 免疫学 / 核酸
Outline of Final Research Achievements

In this study, I tried to elucidate the factors affecting the therapeutic efficacy of TLR3 adjuvant among different tumors. In the previous study, I elucidated that the expression levels of PD-L1, which is immunosuppressive molecule, and MHC class I molecule on each tumor cell affect the therapeutic efficacy. In the present study, We elucidated that the PD-L1 expression level on tumor-infiltrating immune cells are different among various types of tumor-bearing mice. We also showed that the co-administration of anti-PD-L1 antibody enhance the efficacy of TLR3 adjuvant+tumor antigen therapy. This finding has been published on an academic journal.

Academic Significance and Societal Importance of the Research Achievements

近年、宿主の免疫機能の活性化ががんの退縮に重要であることが明らかとなり、抗腫瘍免疫療法が盛んに研究されるようになった。しかし、抗腫瘍免疫療法が奏功する患者が存在する一方、治療効果が認められない患者も一定数存在している。本研究では、異なる腫瘍種においてどのような要因が免疫賦活剤であるTLR3アジュバント療法に対する治療奏功性に影響を与えるかを解析した。本研究は抗腫瘍免疫療法が適用可能な患者における奏功率を上昇させるのみならず、これまで適用不可であった患者にも広く治療を提供するための学術的知見の蓄積に寄与するものである。

Report

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

    (5 results)

All 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models.2018

    • Author(s)
      Takeda Y, Yoshida S, Takashima K, Ishii‐Mugikura N, Shime H, Seya T, Matsumoto M.
    • Journal Title

      Cancer science

      Volume: 109 Issue: 7 Pages: 2119-2129

    • DOI

      10.1111/cas.13649

    • NAID

      120006502508

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] TLR3特異的な抗腫瘍アジュバントであるARNAXは効果的に腫瘍を退縮させ、免疫記憶を誘導する。2018

    • Author(s)
      武田洋平、松本美佐子、瀬谷司
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Noninflammatory adjuvant that improves dendritic cell priming and anti-PD-L1 efficacy.2017

    • Author(s)
      Tsukasa Seya, Yohei Takeda, Misako Matsumoto.
    • Organizer
      The 36th Sapporo International Cancer Symposium (札幌市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 非炎症性TLR3アジュバントARNAXはPD-L1阻害抗体の抗腫瘍効果を増強する。2017

    • Author(s)
      武田洋平、瀬谷司、松本美佐子
    • Organizer
      第21回 日本がん免疫学会総会 (千葉市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] ARNAX, non-inflammatory TLR3 adjuvant, induces tumor-specific CTLs and enhances PD-L1 blockade efficacy.2017

    • Author(s)
      Yohei Takeda, Keisuke Kataoka, Seishi Ogawa, Misako Matsumoto, Tsukasa Seya.
    • Organizer
      第76回 日本癌学会学術総会 (横浜市)
    • Related Report
      2017 Annual Research Report

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Published: 2017-08-25   Modified: 2020-03-30  

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