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Regeneration of T cells specific for cancer antigen using iPSC and genome editing technology

Research Project

Project/Area Number 18K16113
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyoto University

Principal Investigator

Nagano Seiji  京都大学, ウイルス・再生医科学研究所, 特定研究員 (90618018)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords再生T細胞 / がん免疫細胞療法 / CTL / TCR遺伝子 / iPS細胞 / ゲノム編集技術 / 再生医療 / RMCE / 再生CTL / がん抗原特異的TCR遺伝子 / T細胞療法 / 免疫学 / がん / がん免疫療法 / T細胞輸注 / iPS細胞からT細胞への再生
Outline of Final Research Achievements

We have developed a novel immuno-cell therapy in which cancer-specific T cells can be mass-generated from iPS cells that we transduce with cencer antigen-specific T cell receptor (TCR) genes using genome editing techonolgy. In paticular, a cassette deck structure was knocked in (cKI-iPSC) at the TCR locus of the iPSC, and then the exogenous TCR genes were replaced on that cKI-iPSC using the Cre system. We succeeded in inducing regenerated CTLs from these TCR-KI-iPSCs, and confirmed that each had antigen-specific killing activity against cancer cells.

Academic Significance and Societal Importance of the Research Achievements

iPS細胞技術を用いてがん細胞に有効なキラーT細胞を量産できることを示してきました。T細胞を細胞製剤として使うという可能性を大きく広げるものです。しかし、そのことが可能な品質のよいiPS細胞株を作製し同定するには長期間を有することも判明しています。ゲノム編集技術を用いて再生医療用のiPS細胞にがんに特異的な受容体遺伝子を導入することで、上記の問題を解決できないか検証し技術的に可能であることがわかりました。

Report

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

    (4 results)

All 2020 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] High Frequency Production of T Cell-Derived iPSC Clones Capable of Generating Potent Cytotoxic T Cells2020

    • Author(s)
      Nagano Seiji、Maeda Takuya、Ichise Hiroshi、Kashima Soki、Ohtaka Manami、Nakanishi Mahito、Kitawaki Toshio、Kadowaki Norimitsu、Takaori-Kondo Akifumi、Masuda Kyoko、Kawamoto Hiroshi
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 16 Pages: 126-135

    • DOI

      10.1016/j.omtm.2019.12.006

    • NAID

      120007169386

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] iPS細胞技術を用いたがん抗原特異的T細胞の再生2019

    • Author(s)
      永野誠治
    • Organizer
      日本がん免疫学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Generation of CTLs from iPSCs transduced with TCR genes: development of “TCR cassette” method2019

    • Author(s)
      永野誠治
    • Organizer
      日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 外来抗原レセプター遺伝子導入細胞の製造方法2019

    • Inventor(s)
      河本宏, 縣保年, 永野誠治, 寺田晃士, 増田喬子
    • Industrial Property Rights Holder
      河本宏, 縣保年, 永野誠治, 寺田晃士, 増田喬子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas

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Published: 2018-04-23   Modified: 2021-02-19  

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