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A novel strategy for a cancer immunotherapy and infectious disease treatment using microbial antigen-presenting exosomes

Research Project

Project/Area Number 16K01394
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionOsaka Prefecture University

Principal Investigator

Koyama Yoshiyuki  大阪府立大学, 生命環境科学研究科, 客員研究員 (00162090)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsエクソソーム / 人工ネオ抗原 / 結核菌抗原 / 抗腫瘍免疫 / 細胞性免疫 / 感染症 / 人工ネオアンティジェン / 人工ネオエピトープ / 樹状細胞 / 抗腫瘍免疫治療 / ESAT-6 / 免疫治療 / ネオアンティジェン / ネオエピトープ / 微生物抗原 / 免疫学 / バイオテクノロジー / ナノバイオ
Outline of Final Research Achievements

We have developed a novel "artificial neoantigen strategy", where we transformed the tumor cells with a gene encoding for a highly antigenic microbial antigen to induce the protein as an "artificial neoantigen". In vivo transfection with the gene for Mycobacterium tuberculosis antigen, ESAT-6 into tumor cells resulted in a significant inhibition of tumor growth in mice and dogs by both the early innate and following adaptive cellular immune responses.
Transfected tumor cells would secrete exosomes presenting ESAT-6 epitopes (ESAT-Ex). ESAT-Ex would most likely mediate these immune responses. Then we prepared ESAT-Ex from the cultured tumor cells which had been transfected with DNA expressing ESAT-6. Injection of ESAT-Ex into tumor-bearing mice evidently suppressed the tumor growth. Dendritic cells (DCs) were effectively stimulated by ESAT-Ex, and the cultured DCs treated with the exosomes exhibited significantly improved antitumor activity in tumor-bearing mice.

Academic Significance and Societal Importance of the Research Achievements

腫瘍抗原の免疫原性の低さがガン免疫治療の大きな障壁となっている。本研究は、抗原性の高い微生物抗原を人工ネオ抗原として導入し、この障壁を克服する新たな戦略を提供する。
本研究で創製するエクソソーム製剤はウイルス等を含まない安全な生物製剤である。また、より安全なシステムとして、培養樹状細胞を本エクソソーム製剤で活性化し、樹状細胞のみを患者に戻す新たな治療法を考案しその効果を確認した。さらに同システムは感染症治療にも有効な細胞性免疫活性化機能を持つことを確認した。これらの知見は行き詰まったガン免疫治療を大きく推進させるブレイクスルーとなり、感染症の新しい治療法を提示して国民の福祉、健康に貢献する。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (21 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Innate immunity mediated by dendritic cells/macrophages plays a central role in the early period in tumor treatment using gene of Mycobacterium tuberculosis antigen2018

    • Author(s)
      Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K. Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 2 Pages: 190-196

    • DOI

      10.1292/jvms.17-0466

    • NAID

      130006339616

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.2016

    • Author(s)
      Koyama Y, Ito T, Hasegawa A, Eriguchi M, Inaba T, Ushigusa T, Sugiura K.
    • Journal Title

      Biotechnol Lett

      Volume: 38 Issue: 11 Pages: 1857-1866

    • DOI

      10.1007/s10529-016-2185-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] "Artificial neoantigen"-transfection induced significant inhibition of tumor growth by eliciting innate immunity in the early period in tumor treatment2019

    • Author(s)
      Yoshiyuki Koyama, Kikuya Sugiura, Aya Hasegawa, Wakana Ouchi, Toshio Inaba, Masazumi Eriguchi, Tomoko Ito
    • Organizer
      遺伝子・デリバリー研究会第19回シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Preparation of "artificial neoepitope"-presenting exosomes and their ability to stimulate antitumor immunity2019

    • Author(s)
      Tomoko Ito, Kikuya Sugiura, Aya Hasegawa, Wakana Ouchi, Toshio Inaba, Masazumi Eriguchi, Yoshiyuki Koyama
    • Organizer
      遺伝子・デリバリー研究会第19回シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mechanism of antitumor immunity activation by "artificial neoantigen"-presenting exosomes2019

    • Author(s)
      Yoshiyuki Koyama, Tomoko Ito, Masazumi Eriguchi, Aya Hasegawa, Wakana Ouchi, Toshio Inaba, Kikuya Sugiura
    • Organizer
      ISEV2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「人工ネオエピトープ」提示エクソソームの調製と抗腫瘍ワクチンへの応用2019

    • Author(s)
      小山義之、伊藤智子、杉浦喜久弥、大内若菜、長谷川綾、稲葉俊夫、江里口正純
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エクソソームを用いた抗原提示細胞への結核菌抗原エピトープ/MHC Class I分子複合体の送達とその抗腫瘍免疫誘導効果2019

    • Author(s)
      伊藤智子、杉浦喜久弥、大内若菜、長谷川綾、稲葉俊夫、江里口正純、小山義之
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Antitumour immune activation by "artificial neoantigen"-presenting exosomes derived from the genetically modified cells Wakana Ouchi, Toshio Inaba, Kikuya Sugiura2019

    • Author(s)
      Yoshiyuki Koyama, Tomoko Ito, Masazumi Eriguchi, Aya Hasegawa, Wakana Ouchi, Toshio Inaba, Kikuya Sugiura
    • Organizer
      European Society of Gene and Cell Therapy 27th annual congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of "Artificial neoepitope"-presenting exosomes for novel cancer immunotherapy2019

    • Author(s)
      Tomoko Ito, Masazumi Eriguchi, Aya Hasegawa, Wakana Ouchi, Toshio Inaba, Kikuya Sugiura, Yoshiyuki Koyama
    • Organizer
      European Society of Gene and Cell Therapy 27th annual congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 結核菌抗原を「人工ネオアンティジェン」として提示したエクソソームによる抗腫瘍免疫活性化のメカニズム2019

    • Author(s)
      小山義之、伊藤智子、長谷川綾、大内若菜、稲葉俊夫、江里口正純、杉浦喜久弥
    • Organizer
      第16回日本免疫治療学研究会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 「人工ネオエピトープ」を提示したエクソソームを用いたガン免疫治療―免疫治療の新たなブレイクスルーを目指してー2019

    • Author(s)
      小山義之
    • Organizer
      ヒトと伴侶動物の比較医学研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 「人工ネオエピトープ」提示エクソソームによる抗腫瘍免疫活性化のメカニズム2018

    • Author(s)
      小山義之、伊藤智子、江里口正純、長谷川綾、大内若菜、稲葉俊夫、杉浦喜久弥
    • Organizer
      第5回日本細胞外小胞学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ESAT-6 DNA導入による腫瘍治療効果の免疫組織化学的解析2018

    • Author(s)
      大内若菜、牛草貴博、小山義之、伊藤智子、渡邉謙一、James K. CHAMBERS、内田和幸、金城綾二、鳩谷晋吾、稲葉俊夫、杉浦喜久弥
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 「人工Neoantigen」遺伝子を導入した細胞由来のエクソソームを用いた抗腫瘍免疫治療2018

    • Author(s)
      小山義之、伊藤智子、長谷川綾、杉浦喜久弥、稲葉俊夫、江里口正純
    • Organizer
      第15回日本免疫治療学研究会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 人工Neoantigenによる樹状細胞治療の効果改善2017

    • Author(s)
      小山義之、伊藤智子、長谷川綾、杉浦喜久弥、稲葉俊夫、江里口正純
    • Organizer
      遺伝子・デリバリー研究会第17回シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 「人工ネオエピトープ」提示エクソソームによる樹状細胞の活性化と抗腫瘍効果の向上2017

    • Author(s)
      小山義之、伊藤智子、江里口正純、長谷川綾、稲葉俊夫、杉浦喜久弥
    • Organizer
      第4回日本細胞外小胞学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Artificial neoepitope-presenting exosomes derived from the cells genetically modified to express Mycobacterium tuberculosis antigen as cellular immunity adjuvants2017

    • Author(s)
      Tomoko Ito, Kikuya Sugiura, Aya Hasegawa, Toshio Inaba, Masazumi Eriguchi, Yoshiyuki Koyama
    • Organizer
      the 25th Anniversary Congress of the European Society for Gene and Cell Therapy
    • Related Report
      2017 Research-status Report
  • [Presentation] Dendritic cell activation induced by Artificial neoepitope-presenting exosomes derived from the genetically modified cells2017

    • Author(s)
      Yoshiyuki Koyama, Tomoko Ito, Masazumi Eriguchi, Aya Hasegawa, Toshio Inaba, Kikuya Sugiura
    • Organizer
      the 25th Anniversary Congress of the European Society for Gene and Cell Therapy
    • Related Report
      2017 Research-status Report
  • [Presentation] 「人工Neoantigen」遺伝子を導入した細胞由来のエクソソームを用いた抗腫瘍免疫治療2017

    • Author(s)
      小山 義之、伊藤 智子、長谷川 綾、杉浦 喜久弥、稲葉 俊夫、江里口 正純
    • Organizer
      第14回日本免疫治療学研究会
    • Place of Presentation
      東京大学 伊藤国際学術研究センター
    • Related Report
      2016 Research-status Report
  • [Presentation] "Artificial neoepitope"-bearing exosomes as novel vaccine for cancer immunotherapy2016

    • Author(s)
      Yoshiyuki Koyama, Tomoko Ito, Kikuya Sugiura, Toshio Inaba
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] 「人工ネオエピトープ」を担持した腫瘍由来エクソソームによるガン免疫治療2016

    • Author(s)
      小山義之、伊藤智子、長谷川綾、杉浦 喜久弥、稲葉俊夫、江里口正純
    • Organizer
      第3回日本細胞外小胞学会
    • Place of Presentation
      グランドプリンスホテル広島
    • Year and Date
      2016-08-31
    • Related Report
      2016 Research-status Report
  • [Presentation] "Artificial neoepitope"- bearing exosomes derived from tumor cells being genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy2016

    • Author(s)
      Koyama Yoshiyuki, Ito Tomoko, Eriguchi Masazumi, Hasegawa Aya, Inaba Toshio, Sugiura Kikuya
    • Organizer
      5th Annual Meeting of the International Society for Extracellular Vesicles
    • Place of Presentation
      Rotterdam, the Netherlands
    • Year and Date
      2016-05-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 人工Neoepitopeを担持したエクソソームを用いた抗腫瘍免疫治療2016

    • Author(s)
      小山義之、伊藤智子、長谷川綾、杉浦 喜久弥、稲葉俊夫、江里口正純
    • Organizer
      第16回遺伝子・デリバリー研究会シンポジウム
    • Place of Presentation
      川崎生命科学・環境研究センター
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 免疫治療システム2016

    • Inventor(s)
      小山 義之
    • Industrial Property Rights Holder
      小山 義之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-219198
    • Filing Date
      2016-10-24
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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