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Affinity maturation of cancer-specific TCRs by in vitro cell display methods and their application to drug discovery.

Research Project

Project/Area Number 18K07285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionNagoya City University

Principal Investigator

OHTA RIEKO  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (30452460)

Co-Investigator(Kenkyū-buntansha) 葛島 清隆  愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, 分野長 (30311442)
今井 優樹  名古屋市立大学, 医薬学総合研究院(医学), 講師 (30440936)
岡村 文子 (出町文子)  愛知県がんセンター(研究所), 腫瘍免疫制御TR分野, 主任研究員 (10546948)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsT細胞受容体 / 親和性の成熟 / がん特異的TCR / 膜侵襲複合体 / 補体 / T細胞受容体 / TCR
Outline of Final Research Achievements

In cancer patients, despite the expression of cancer-specific antigens in cancer tissue, serum antibody titers against cancer are low and the frequency of cancer-specific cytotoxic T cells (CTL, killer T cells) is low. In this study, we demonstrated the potential for in vitro affinity maturation of HLA-A24-restricted, which are present in approximately 60% of the Japanese population, cancer antigen-specific CTL clones using the 'method of TCR display system using 293T cells '. We were also able to construct a single chain variable fragment (scFv) that induces the formation of membrane attack complexes. Linking this scFv with high-affinity TCR mutants could lead to the development of new therapeutic reagents.

Academic Significance and Societal Importance of the Research Achievements

日本人の大多数が有するHLA拘束性のがん抗原を認識するCTLクローンのTCRから、抗原に高親和性のTCRが取得できれば、日本人に適した新たながんのターゲティングが可能になると考えられる。今回、「293T細胞ディスプレイ法」を用いて、一価での親和性が低いTCRについて、高親和性TCRの取得に成功した。今後、この技術が応用され、種々のがん抗原に対する高親和性TCR を用いた薬剤の創製に寄与すると考えられる

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Improving TCR affinity on 293T cells2019

    • Author(s)
      Ohta Rieko、Demachi-Okamura Ayako、Akatsuka Yoshiki、Fujiwara Hiroshi、Kuzushima Kiyotaka
    • Journal Title

      Journal of Immunological Methods

      Volume: 466 Pages: 1-8

    • DOI

      10.1016/j.jim.2018.11.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規活性型カルボキシペプチダーゼRの一次構造予測2020

    • Author(s)
      河村 剛至、太田 里永子 、山本 博之、今井 優樹、安野 伸浩
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Expression of complement anaphylatoxin receptor in the various subsets of dendritic cells2019

    • Author(s)
      Masaki Imai, Rieko Ohta, Sayuri Yamazaki
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト培養細胞を用いたTCR親和性成熟システムの樹立2018

    • Author(s)
      太田里永子、岡村 文子、赤塚 美樹、葛島 清隆
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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