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Novel DNA vaccine strategy to elicit antitumor immune responses by transfecting with plasmids coding for pathogenic antigens

Research Project

Project/Area Number 26350533
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 (2016)
Meiji Pharmaceutical University (2014-2015)

Principal Investigator

Ito Tomoko  大阪府立大学, 生命環境科学研究科, 客員研究員 (80372910)

Co-Investigator(Renkei-kenkyūsha) KOYAMA Yoshiyuki  大阪府立大学, 生命環境科学研究科, 客員研究員 (00162090)
Research Collaborator ERIGUCHI Masazumi  
USHIGUSA Takahiro  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsDNAワクチン / 遺伝子治療 / ガン免疫治療
Outline of Final Research Achievements

We have developed a novel antitumor strategy by transfecting with the plasmids coding for pathogenic antigens. We examined the therapeutic effects of the transfection of the plasmid coding a membrane-associating protein, ESAT-6, or a secretory antigen, Ag85B. Both plasmids showed similar significant effects in tumor-bearing mice. Accumulation of T-cells and monocytic cells was observed in the diminished tumors. The antigens synthesized in the tumor cells would be degraded as heterologous proteins, and the degraded peptides would be presented on the cell surfaces as "artificial neoepitopes". The exosomes presenting the epitopes would be secreted from the cells, and were thought to play an essential role in eliciting antitumor immunity. This hypothesis was confirmed by the experiments with the exosomes presenting the "artificial neoepitopes", which had been prepared by transfection of the cultured cells with the pathogenic antigen genes.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report

Research Products

(16 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Effect of pDNA complex particle size on gene expression: difference between in vitro and in vivo experiments2016

    • Author(s)
      Tomoko Ito, Masazumi Eriguchi, Yoshiyuki Koyama
    • Journal Title

      Journal of Nanomaterials & Molecular Nanotechnology

      Volume: 5 Pages: 1-5

    • DOI

      10.4172/2324-8777.1000202

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

      Biotechnology Letters

      Volume: 38 Pages: 1857-1866

    • DOI

      10.1007/s10529-016-2185-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Highly effective non-viral antitumor gene therapy system comprised of biocompatible small plasmid complex particles consisting of pDNA, anionic polysaccharide, and fully deprotected linear polyethylenimine2015

    • Author(s)
      Yoshiyuki Koyama, Kikuya Sugiura, Chieko Yoshihara, Toshio Inaba, Tomoko Ito
    • Journal Title

      Pharmaceutics

      Volume: 7 Pages: 152-164

    • DOI

      10.3390/pharmaceutics7030152

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel antitumor strategy by transfection of plasmid expressing mycobacterium tuberculosis antigen as a "Danger Signal" to block immune escape of tumor cells2015

    • Author(s)
      Yoshiyuki Koyama, Chieko Yoshihara, Tomoko Ito
    • Journal Title

      Pharmaceutics

      Volume: 7 Pages: 165-174

    • DOI

      10.3390/pharmaceutics7030165

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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学術集会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2017-02-11
    • Related Report
      2016 Annual Research 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(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research 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(広島県広島市)
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 人工Neoantigen(新抗原)遺伝子を用いた抗腫瘍免疫治療システムの創製2016

    • Author(s)
      伊藤智子、長谷川綾、牛草貴博、杉浦喜久弥、稲葉俊夫、江里口正純、小山義之
    • Organizer
      遺伝子・デリバリー研究会第16回シンポジウム
    • Place of Presentation
      川崎生命科学・環境研究センター(神奈川県川崎市)
    • Year and Date
      2016-05-16
    • Related Report
      2016 Annual Research Report
  • [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
      遺伝子・デリバリー研究会第16回シンポジウム
    • Place of Presentation
      川崎生命科学・環境研究センター(神奈川県川崎市)
    • Year and Date
      2016-05-16
    • Related Report
      2016 Annual Research 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)
      Yoshiyuki Koyama, Tomoko Ito, Eriguchi Masazumi, Aya Hasegawa, Toshio Inaba, Kikuya Sugiura
    • Organizer
      the 5th Annual Meeting of International Society for Extracellular Vesicles
    • Place of Presentation
      De Doelen International Congress Centre, Rotterdam, The Netherlands
    • Year and Date
      2016-05-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 結核菌抗原遺伝子を用いた新規抗腫瘍DNAワクチンの創製2015

    • Author(s)
      伊藤智子、牛草貴博、杉浦喜久弥、稲葉俊夫、江里口正純、小山義之
    • Organizer
      第37回日本バイオマテリアル学会大会
    • Place of Presentation
      京都テルサ(京都・京都)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Preparation and therapeutic effect of calcium phosphate nano-capsules enclosing DNA/PEI/hyaluronic acid complex for durable gene expression2015

    • Author(s)
      Tomoko Ito, Yoshiyuki Koyama, Masazumi Eriguchi, Makoto Otsuka
    • Organizer
      27th European Conference on Biomaterials
    • Place of Presentation
      Kraków (POLAND)
    • Year and Date
      2015-08-31
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA complex release system by injectable auto-forming alginate gel including amorphous calcium phosphate2015

    • Author(s)
      Tomoko Ito, Yoshiyuki Koyama
    • Organizer
      the 2015 Society For Biomaterials Annual Meeting & Exposition
    • Place of Presentation
      North Carolina (USA)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development and Therapeutic Efficacy of the DNA Complex-Releasing Systems Comprising Injectable Auto-Forming Alginate Gel2014

    • Author(s)
      Tomoko Ito, Yoshiyuki Koyama
    • Organizer
      ESGCT and NVGCT Collaborative Congress
    • Place of Presentation
      World Forum, The Hague, Netherlands
    • Year and Date
      2014-10-23 – 2014-10-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Oncolytic Plasmid System; a Novel Antitumor Strategy by Plasmids Encoding Pathogenic Antigens Blocking the Immune Escape of Tumor2014

    • Author(s)
      Yoshiyuki Koyama, Takahiro Ushigusa, Toshio Inaba, Kikuya Sugiura, Masazumi Eriguchi, Tomoko Ito
    • Organizer
      ESGCT and NVGCT Collaborative Congress
    • Place of Presentation
      World Forum, The Hague, Netherlands
    • Year and Date
      2014-10-23 – 2014-10-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 生分解性生体接着材料の開発と止血材・癒着防止材への応用2014

    • Author(s)
      小山義之、江里口正純、伊藤智子
    • Organizer
      第63回高分子討論会
    • Place of Presentation
      長崎大学文教キャンパス
    • Year and Date
      2014-09-24 – 2014-09-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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