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Development of a cell therapy for autoimmune diseases using monoclonal T cells specific for one target antigen

Research Project

Project/Area Number 18H02668
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionKyoto University

Principal Investigator

kawamoto hiroshi  京都大学, ウイルス・再生医科学研究所, 教授 (00343228)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords制御性T細胞 / 自己免疫疾患 / 関節リウマチモデル / sk gマウス / RPL23a / 関節リウマチ / T細胞レセプター / クローン / iPS細胞 / 間接リウマチ
Outline of Final Research Achievements

In this study, we tried to develop a new method by which autoimmune diseases can be cured using a monoclonal T cells with single antigen specificity. It has been reported that the monoclonal helper T cells expressing TCR (R7-39) specific for target antigen originally identified as a causative antigen of arthritis and dermatitis in skg mouse. Therefore, in this study, we produced regulatory T cells (Treg) that monoclonally express TCR (R7-39) and tested whether these cells exert therapeutic effect on the desiase model described above. We found that, although adaptive transfer of these cells were not effective for arthritis, these cells showed efficacy in reducing the severity of dermatitis. This can be said as a first demonstration in the world that showed treatment of disease by using Treg. Some planned experiments were not necessarily completed as originally designed, but we can say that a significant results were obtained during the study period.

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患の治療は、免疫抑制剤や抗サイトカイン抗体などで免疫を非特異的に抑制するという方法が現在も主流であり、従って感染症などの副作用が避けられない。このような状況を打開するためには、抗原特異的な治療法で特定の標的抗原に対する免疫反応だけを抑えて病気を治す必要がある。本研究はそのような方法の開発に取り組んだ先進的な取り組みであった。その結果として、単一クローンのヘルパーT細胞で誘導できる皮膚炎が、同じ抗原特異性を持つ単一クローン制御性T細胞の投与により症状を軽減できることが示された。制御性T細胞による発症予防の報告は多くあるが、治療例としては世界初であると考えている。

Report

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

    (20 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 1 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 13 results)

  • [Journal Article] Possible NK cell-mediated immune responses against iPSC-derived cells in allogeneic transplantation settings2021

    • Author(s)
      Masuda K and Kawamoto H
    • Journal Title

      Inflamm Regener

      Volume: 41 Pages: 2-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 再生医療と移植免疫 : iPS細胞由来再生細胞を他家移植で用いたときに起こりうる免疫反応2021

    • Author(s)
      増田喬子
    • Journal Title

      医学のあゆみ

      Volume: 765 Pages: 809-817

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 再生医療と免疫 : iPS細胞由来「他家」再生細胞に起こりうる免疫反応2021

    • Author(s)
      河本宏
    • Journal Title

      再生医療 : 日本再生医療学会雑誌

      Volume: 20 Pages: 16-32

    • NAID

      40022522930

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] 免疫応答の基本的な仕組み2020

    • Author(s)
      河本宏
    • Journal Title

      小児科臨床

      Volume: 73 Pages: 1707-1715

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 特別寄稿2018年度ノーベル生理学・医学賞解説─免疫チェックポイント阻害剤の作用機序と開発過程2019

    • Author(s)
      河本宏
    • Journal Title

      生物の科学遺伝

      Volume: 100 Pages: 4-12

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Cloning and expansion of antigen-specific T cells using iPS cell technology: Possible use of regenerated T cells in personalized medicine2018

    • Author(s)
      Kawamoto, H., Masuda, K., Nagano, S.
    • Journal Title

      Personalized Medicine Universe

      Volume: 7 Pages: 7-12

    • Related Report
      2018 Annual Research Report
  • [Presentation] 他家再生細胞を用いた時に起こりうる免疫反応とその頻度の予測2021

    • Author(s)
      河本 宏
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来再生細胞を他家移植で用いたときに起こりうる免疫反応とその制御法の開発2021

    • Author(s)
      増田 喬子
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 腫瘍免疫学の基礎と臨床-即納型T細胞製剤の開発-2019

    • Author(s)
      河本宏
    • Organizer
      第4回日本骨免疫学会ウィンターセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] よくわかる免疫学:獲得免疫編2019

    • Author(s)
      河本宏
    • Organizer
      第2回日本免疫不全・自己炎症学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 再生医療とがん免疫療法の現状と問題点 ー再生T細胞を用いたがんの免疫細胞療法の開発ー2019

    • Author(s)
      河本宏
    • Organizer
      第37回耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regeneration of antigen-specific T cells using the iPSC technology.2019

    • Author(s)
      Kawamoto, H.
    • Organizer
      第2回AMED-A*STAR合同ワークショップ-Stem Cell & Immune Cell Therapy-
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いたがん抗原特異的CTLの量産-即納型T細胞製剤の開発に向けて-2019

    • Author(s)
      河本宏
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いたがん抗原特異的キラーT細胞の再生 -他家移植の系で使える即納T細胞製剤の開発-2018

    • Author(s)
      河本宏
    • Organizer
      第28回日本サイトメトリー学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いたWT1抗原特異的キラーT細胞の作製 -他家移植の系で使える即納T細胞製剤の開発-2018

    • Author(s)
      河本宏
    • Organizer
      日本免疫・細胞治療セミナー2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いたがん抗原特異的キラーT細胞の再生 -他家移植の系で使える即納T細胞製剤の開発-2018

    • Author(s)
      河本宏
    • Organizer
      第5回神戸血液疾患症例検討会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いたがん抗原特異的キラーT細胞の再生 -他家移植の系で使える即納T細胞製剤の開発-2018

    • Author(s)
      河本宏
    • Organizer
      再生医療エキスパートレクチャー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regeneration of antigen-specific T cells using the iPS cell technology2018

    • Author(s)
      Kawamoto, H.
    • Organizer
      The 1st International Symposium on NEO-SELF
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS細胞技術を用いたがん抗原特異的キラーT細胞の再生 -他家移植用“off-the-shelf”T細胞製剤の開発-2018

    • Author(s)
      河本宏
    • Organizer
      第18回神戸がん研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いたがん抗原特異的CTLの量産 -即納型T細胞製剤の開発に向けて-2018

    • Author(s)
      河本宏
    • Organizer
      第46回日本臨床免疫学会総会
    • Related Report
      2018 Annual Research Report
    • Invited

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

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