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Rapid cloning of tumor reactive TCR genes for personalized TCR-T cell therapy

Research Project

Project/Area Number 18K07260
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 InstitutionUniversity of Toyama

Principal Investigator

Hamana Hiroshi  富山大学, 学術研究部医学系, 助教 (90551549)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsT細胞受容体 / TCR-T細胞療法 / TCR / ネオ抗原 / ネオアンチゲン / がん免疫療法 / 腫瘍浸潤リンパ球 / T細胞受容体(TCR) / Jurkat細胞 / Luciferaseアッセイ / 機能解析 / Luciferase assay / Jurkat / TAP / T細胞受容体(TCR) / WT1 / TCR遺伝子 / がん浸潤リンパ球(TIL) / T細胞受容体(TCR) / 個別化免疫療法
Outline of Final Research Achievements

Currently, immune checkpoint inhibitors and CAR-T cell therapy are approved for some cancers, and expectations for cancer immunotherapy are increasing. One of the promising cancer immunotherapies in the future is TCR-T cell therapy. This therapy uses TCR-T cells generated by gene transfer of cancer-specific TCR genes into T cells. However, obtaining the cancer-specific TCR gene required for the generation of TCR-T cells has been a time-consuming and labor-intensive work.
In this study, we developed a rapid and simple method to obtain the cancer-specific TCR gene, which is necessary for TCR-T cell therapy. This method is expected to facilitate the development and research of TCR-T cell therapy.

Academic Significance and Societal Importance of the Research Achievements

がん患者から得られたTCR遺伝子が、がん特異的TCR遺伝子であるかを解析するために、従来法ではヒトやマウスから採取した細胞を用いて実験を行っていましたが、それらの細胞の調製には時間と労力が必要でした。そこで、本研究では、簡単に培養できる培養細胞株を用いてTCRの機能を迅速・簡便に解析する方法を開発しました。そして、その方法を用いて、大腸がん患者からネオ抗原(がん細胞特有の遺伝子変異に由来するがん抗原)に特異的なTCR遺伝子の取得に成功しました。従って、本研究の成果は、個別化されたTCR-T細胞療法に有用なTCR遺伝子取得に貢献し、新たながん免疫療法の発展に寄与することが期待されます。

Report

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

    (7 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Identification of Novel HLA Class II-Restricted Neoantigens Derived from Driver Mutations2019

    • Author(s)
      Iiizumi Susumu、Ohtake Junya、Murakami Naoko、Kouro Taku、Kawahara Mamoru、Isoda Fumiko、Hamana Hiroshi、Kishi Hiroyuki、Nakamura Norihiro、Sasada Tetsuro
    • Journal Title

      Cancers

      Volume: 11 Issue: 2 Pages: 266-266

    • DOI

      10.3390/cancers11020266

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Jurkat細胞を用いたTCRのネオアンチゲン反応性解析2020

    • Author(s)
      浜名 洋, 宮原 慶裕, 祐川 健太, 下岡 清美, 小林 栄治, 小澤 龍彦, 村口 篤, 藤井 努, 珠玖 洋, 岸 裕幸
    • Organizer
      第24回日本がん免疫学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 患者HLA遺伝子導入乳がん細胞株を用いた乳がん患者TIL中の腫瘍反応性TCRの探索2019

    • Author(s)
      浜名 洋、下岡清美、祐川健太、佐伯しおり、長田任一哉、小林栄治、小澤龍彦、藤井 努、村口 篤、岸 裕幸
    • Organizer
      第23回 日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腫瘍浸潤CD8+ T細胞におけるPD-1の発現はTCRレパトアに規定される2019

    • Author(s)
      祐川健太、佐伯しおり、下岡清美、浜名 洋、宮原慶裕、小林栄治、長田任一哉、小澤龍彦、藤井 努、珠玖 洋、村口 篤、岸 裕幸
    • Organizer
      第23回 日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Screening of tumor-reactive TCRs from TILs of breast cancer patients using a patients’ HLA-transduced breast cancer cell line2019

    • Author(s)
      Hiroshi Hamana, Kiyomi Shitaoka, Kenta Sukegawa, Shiori Saeki, Takuya Nagata, Eiji Kobayashi, Tatsuhiko Ozawa, Tsutomu Fujii, Atsushi Muraguchi, Hiroyuki Kishi
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] A new epitope is identified derived from envelope protein of an endogenous murine leukemia virus2019

    • Author(s)
      Kiyomi Shitaoka, Hiroshi Hamana, Atsushi Muraguchi, Hiroyuki Kishi
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] A rapid and simple protocol for cDNA clonig of tumor antigen-specific TCR2018

    • Author(s)
      Hiroshi Hamana, Tatsuhiko Ozawa, Eiji Kobayashi, Kiyomi Shitaoka, Atsushi Muraguchi, Hiroyuki Kishi
    • Organizer
      The 47th Annual Meeting of The Japanese Society for Immunology (福岡, 12/10-12/12)
    • Related Report
      2018 Research-status Report

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

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