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2011 Fiscal Year Final Research Report

Novel Strategy of Tumor Gene Therapy by Very Small Plasmid Complex Particles

Research Project

  • PDF
Project/Area Number 21500430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionOtsuma Women's University

Principal Investigator

KOYAMA Yoshiyuki  大妻女子大学, 家政学部, 教授 (00162090)

Co-Investigator(Renkei-kenkyūsha) YOSHIHARA Chieko  大妻女子大学, 家政学部, 助手 (40597093)
Project Period (FY) 2009 – 2011
Keywords薬物伝達システム
Research Abstract

Great efforts have been focused on developing the non-viral vector systems as safer alternatives to viruses. But the in vivo gene expression by those artificial vectors is strictly limited. The major obstacles should be adverse interactions of the complex with biocomponents, and the too large size of the complexes to be delivered to the target cells. We developed an anionic polymer-coating on the complex particles, which re-charged the particles to negative, and effectively diminished the non-specific interactions. It also enabled the preparation of concentrated very small DNA complex suspension under the precise conditions.
Small plasmid complexes were then prepared with the PEI and the plasmids encoding cytokines or virus specific proteins, and explored for anticancer therapeutic potential with tumor-bearing mice. They showed significant therapeutic effect in mice after intratumoral injection, and fairly high therapeutic effect was obtained.
In order to induce higher immune response to tumor cells, expression of the pathogenic antigen on the tumor cell surface should be effective. Simultaneous transfection with plasmids expressing cytokines and pathogenic antigen into tumor cells should, thus, be expected to lead to highly effective anti-tumor immune-enhancement.
We employed two pathogenic proteins, adenovirus death protein(ADP) and mycobacterium tuberculosis early secretory antigenic target-6 protein(ESAT-6), and mycobacterium tuberculosis major secretory protein antigen 85B(Ag85B) as an immune response-inducing antigen. The small complexes made of the plasmids harboring the pathogenic protein genes showed highly effective anti-tumor activity, and as expected, co-transfection of those pathogenic genes with cytokine-genes induced much higher anti-tumor therapeutic effect in tumor-bearing mice. Animal clinical study on primary tumor-bearing dogs was also carried out, and evident suppression of the tumor growth was observed.

  • Research Products

    (10 results)

All 2012 2011 2010

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Oncolytic plasmid : A novel strategy for tumor immuno-gene therapy2012

    • Author(s)
      Yoshihara C., Hamada K., Kuroda M., Koyama Y.
    • Journal Title

      Oncology Letters

      Volume: 3 Pages: 387-390

    • Peer Reviewed
  • [Journal Article] Antitumor effect of chondroitin sulfate-coated ternary granulocyte macrophage-colony-stimulating factor plasmid complex for ovarian cancer2012

    • Author(s)
      Hamada K., Yoshihara C., Ito T., Tani K., Tagawa M., Sakuragawa N., Itoh H., Koyama Y.
    • Journal Title

      J Gene Med.

      Volume: 14 Pages: 120-127

    • Peer Reviewed
  • [Journal Article] Loosening of DNA/polycation complexes by synthetic polyampholyte to improve the transcription efficiency : effect of charge balance in the polyampholyte2010

    • Author(s)
      Yoshihara C., Shew C-Y., Ito T., Koyama Y.
    • Journal Title

      Biophys J.

      Volume: 98 Pages: 1257-66

    • Peer Reviewed
  • [Journal Article] DNA/polyethyleneimine/hyaluronic acid small complex particles and tumor suppression in mice2010

    • Author(s)
      Ito T., Yoshihara C., Hamada K., Koyama Y.
    • Journal Title

      Biomaterials

      Volume: 31 Pages: 2912-8

    • Peer Reviewed
  • [Journal Article] Analysis of the surface structure of DNA/polycation/hyaluronic acid ternary complex by Raman microscopy2010

    • Author(s)
      Ito T., Koyama Y., Otsuka M
    • Journal Title

      J Pharm Biomed Anal.

      Volume: 51 Pages: 268-72

    • Peer Reviewed
  • [Presentation] Novel Antitumor Strategy by Transfection of Plasmids Encoding Pathogenic Antigen-and Cytokine-Genes2012

    • Author(s)
      Y. Koyama, C. Yoshihara, T. Ito, and M. Eriguchi
    • Organizer
      American Society of Gene and Cell Therapy
    • Place of Presentation
      Philadelphia
    • Year and Date
      20120500
  • [Presentation] Oncolytic Plasmid System, a Novel Antitumor Strategy by Plasmid Encoding Adenovirus Protein2011

    • Author(s)
      Y. Koyama, M. Tojyo, C. Yoshihara, K. Hamada, and T. Ito
    • Organizer
      American Society of Gene and Cell Therapy
    • Place of Presentation
      Seattle
    • Year and Date
      20110500
  • [Presentation] Small Plasmid/PEI/Anionic Polysaccharide Ternary Complex Particles : Toxicity and Animal Clinical Study2010

    • Author(s)
      Y. Koyama, M. Tojyo, C. Yoshihara, K. Hamada, and T. Ito
    • Organizer
      American Society of Gene and Cell Therapy
    • Place of Presentation
      Washington DC
    • Year and Date
      20100500
  • [Patent(Industrial Property Rights)] 新規な複合体、それを含有する医薬及び癌の治療方法2011

    • Inventor(s)
      小山義之、芳原智恵子
    • Industrial Property Rights Holder
      アルファ・ナノ・メディカ(株)
    • Industrial Property Number
      特許、特願2011-201136
    • Filing Date
      2011-08-29
  • [Patent(Industrial Property Rights)] 新規なベクター、それを含有する医薬及び癌の治療方法2010

    • Inventor(s)
      濱田雄行、小山義之、芳原智恵子、伊藤智子
    • Industrial Property Rights Holder
      アルファ・ナノ・メディカ(株)
    • Industrial Property Number
      特許、特願2010-20766
    • Filing Date
      2010-04-20

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Published: 2013-07-31  

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