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Development of Novel Antitumor DNA Vaccine Utilizing a Plasmid Expressing a Mycobacterium Tuberculosis Antigen

Research Project

Project/Area Number 25350555
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 (2014-2015)
Otsuma Women's University (2013)

Principal Investigator

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

Co-Investigator(Renkei-kenkyūsha) Yoshihara Chieko  大妻女子大学, 家政学部, 助手 (40597093)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords遺伝子治療 / DNAワクチン / 結核菌抗原 / ネオアンティジェン / ネオエピトープ / 抗腫瘍ワクチン / 遺伝子導入 / プラスミド / 免疫治療 / プラスミドDNA / 抗腫瘍効果 / ESAT-6 / Ag85B / デンジャーシグナル / 癌免疫療法 / サイトカイン / DNA複合体 / 結核菌タンパク / 非ウィルスベクター / 抗腫瘍免疫
Outline of Final Research Achievements

For an efficient tumor immunotherapy, mutant neoantigen is required as a target of immune response. We have developed a novel strategy to enhance the antitumor immune response by transfecting the pathogenic microorganism's gene into the tumor cells. It would induce the pathogenic antigen as an "artificial neoantigen" into the tumor cell surfaces, which would be recognized by antigen-presenting cells (APCs) as a "danger signal", and the immune systems would be stimulated.
Here, we employed Mycobacterium tuberculosis antigen ESAT-6 and Ag85B, as danger signal antigens. DNA complexes with ESAT-6- or Ag85B-coding plasmid demonstrated higher anti-tumor effect than those coding cytokine genes such as GM-CSF, or IL12. Co-transfection of the cytokine-genes with the pathogenic antigen genes exhibited good synergistic effect in tumor-bearing mice. Animal clinical study on primary tumor-bearing dogs was also carried out, and a significant a significant reduction of tumor volume was observed.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [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 Issue: 3 Pages: 165-174

    • DOI

      10.3390/pharmaceutics7030165

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Issue: 3 Pages: 152-164

    • DOI

      10.3390/pharmaceutics7030152

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / 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
      日本バイオマテリアル学会
    • Place of Presentation
      京都テルサ、京都市
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tissue-Adhesive Hydrogel for Hemostasis Comprising Water-Swellable Poly(acrylic acid)/Poly(vinylpyrrolidone) Complex2015

    • Author(s)
      Yoshiyuki Koyama, Tomoko Ito, Shingo Yamaguchi, Yoichi Kurachi, Masazumi Eriguchi
    • Organizer
      European Society for Biomaterials
    • Place of Presentation
      ICE Krakow Congress Centre, Cracow, Poland
    • Year and Date
      2015-08-30
    • Related Report
      2015 Annual Research 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
      Society For Biomaterials
    • Place of Presentation
      Charlotte, NC, USA
    • Year and Date
      2015-04-15 – 2015-04-18
    • Related Report
      2014 Research-status Report
  • [Presentation] DNA complex release system by injectable auto-forming alginate gel including amorphous calcium phosphate2015

    • Author(s)
      Tomoko Ito, Yoshiyuki Koyama
    • Organizer
      Society For Biomaterials
    • Place of Presentation
      the Charlotte Convention Center, Charlotte. NC,U SA
    • Year and Date
      2015-04-15
    • Related Report
      2015 Annual Research 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
      European Society for Gene and Cell Therapy
    • Place of Presentation
      The Hague, The 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
      European Society for Gene and Cell Therapy
    • Place of Presentation
      The Hague, The 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
      日本高分子学会高分子討論会
    • 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
  • [Presentation] Novel Adhesive Hemostatic Sponges Comprising PAA/PVP Gel: Preparation and Clinical Application in Dental Surgery2014

    • Author(s)
      Yoshiyuki Koyama, Shingo Yamaguchi, Yoichi Kurachi, Masazumi Eriguchi, Tomoko Ito
    • Organizer
      European Society for Biomaterials
    • Place of Presentation
      Liverpool, UK
    • Year and Date
      2014-08-31 – 2014-09-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of novel biodegradable device forming bioadhesive hydrogel for Hemostatics and adhesion barriers (2): Preparation of the Hemostatic Sponges and Clinical Application in Dental Surgery2014

    • Author(s)
      Yoshiyuki Koyama, Tomoko Ito, Shingo Yamaguchi, Yoichi Kurachi, Masazumi Eriguchi
    • Organizer
      Society For Biomaterials
    • Place of Presentation
      Denver, CO, USA
    • Year and Date
      2014-04-16 – 2014-04-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Gene transfer of chondroitin sulfate-coated granulocyte macrophage-colony stimulating factor in ovarian cancer2013

    • Author(s)
      濱田雄行
    • Organizer
      American Society of Gene & Cell Therapy 2013 Annual Meeting
    • Place of Presentation
      Salt Lake City, Utah
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗原性の強い微生物タンパクをコードしたプラスミド複合体による 新しいガン免疫遺伝子治療戦略2013

    • Author(s)
      芳原智恵子
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 微生物抗原遺伝子導入による抗腫瘍免疫の亢進

    • Author(s)
      芳原智恵子
    • Organizer
      遺伝子・デリバリー研究会第13回シンポジウム
    • Place of Presentation
      帝京大学板橋キャンパス
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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