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Analyses for the enhancing methods of tumor vaccination therapy in cancer-bearing hosts

Research Project

Project/Area Number 18591241
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionUniversity of Yamanashi

Principal Investigator

SHIBAGAKI Naotaka  University of Yamanashi, Dept of Research Interdisciplinary Graduate School of Medicine and Engineering, Associate Professor (40262662)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsVaccine / Antigen-specific immune responses / Antigen presentation / Protein transduction / 免疫療法 / 樹状細胞 / タンパク抗原
Research Abstract

We previously have shown that nona-arginine (R9)-PTD induced efficient protein-antigen (Ag) transduction of dendritic cells (DCs) in vitro, resulting in the efficient induction of strong Ag-specific immune responses mediated by CD8+ and CD4+ T cells and in superior antitumor effects in vivo. In the present study, we investigated the immune responses caused by intradermal (i.d.) injections of R9-PTD-containing protein Ags without DC preparation. We found that i.d. injections of recombinant R9-ovalbumin fusion protein (rR9-OVA) into naive C57BL/6 mice elicited OVA-specific CTLs and produced IgG2-dominant immunoglobulin. The i.d. injections of rR9-OVA also induced inflammatory cell infiltrations containing neutrophils, monocytes, and lymphocytes, as well as inflammatory cytokine productions, such as IFN-gamma, IL-2, IP-10, with presenting SIINFEKL-epitopes on MHC class I molecules at the injection area. Intratumoral injections of rR9-OVA into EG.7-tumor mass significantly suppressed tumor growth, and these effects were completely abrogated by the depletion of CD8+ T cells. These results indicate that i.d. injections of rR9-containing immunogenic Ag simultaneously induce dual immunological effects: the induction of Tc1- and Th1-dominant immune responses, and the induction of inflammatory and CTL-mediated immune responses at the injection area by expressing Ag-epitopes onto MHC class I molecules as targets.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (10 results)

All 2007 2006

All Journal Article (8 results) (of which Peer Reviewed: 3 results) Presentation (2 results)

  • [Journal Article] Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-cell lymphoma.2007

    • Author(s)
      T. Inozume, N. Shibagaki, et. al.
    • Journal Title

      Journal of Investigative Dermatology 127

      Pages: 2818-2822

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human eosinophils have an intact signaling pathway leading to a major transforming growth factor-beta target gene expression.2007

    • Author(s)
      M. Kanzaki, N. Shibagaki, et. al.
    • Journal Title

      International Archives of Allergy and Immunology 142

      Pages: 309-317

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-cell lymphoma2007

    • Author(s)
      T. Inozume, N. Shibagaki, et. al.
    • Journal Title

      Journal of Investigative Dermatology 127

      Pages: 2818-2822

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human eosinophils have an intact signaling pathway leading to a major transforming growth factor-beta target gene expression2007

    • Author(s)
      M. Kanzaki, N. Shibagaki, et. al.
    • Journal Title

      International Archives of Allergy and Immunology 142(4)

      Pages: 309-317

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Polyarginine-mediated protein delivery to dendritic cells presents antigen more efficiently onto MHC class I and class II and elicits superior antitumor immunity.2006

    • Author(s)
      H. Mitsui, N. Shibagaki, et. al.
    • Journal Title

      Journal of Investigative Dermatology 126

      Pages: 1804-1812

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Polyarginine-mediated protein delivery to dendritic cells presents antigen more efficiently onto MHC class I and class II and elicits superior antitumor immunity2006

    • Author(s)
      H. Mitsui, N.Shibagaki, et. al.
    • Journal Title

      Journal of Investigative Dermatology 126(1)

      Pages: 1804-1812

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Polyarginine-mediated protein delivery to dendritic cells presents antigen more efficiently onto MHC class I and class II2006

    • Author(s)
      Mitsui H, Inozume T, Kitamura R, Shibagaki N, shimada S.
    • Journal Title

      Jouranal of Investigative Dermatology 126(8)

      Pages: 1804-12

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Human eosinophils have an intact Smad signaling pathway leading to a major transforming growth factor-beta traget gene expression2006

    • Author(s)
      Kanzaki M, Shibagaki N, Hatsushika K, Mitsui H, Inozume T Okamoto A, Dobashi Y, Ogawa H, Shimada S, Nkao A.
    • Journal Title

      International Archive of Allegy and Immunology 142(4)

      Pages: 309-17

    • Related Report
      2006 Annual Research Report
  • [Presentation] A Novel Vaccination System Utilizing Protein-transduction Domain2007

    • Author(s)
      N. Shibagaki
    • Organizer
      World Congress of Dermatology
    • Place of Presentation
      Buenos Aires(Argentine)
    • Year and Date
      2007-10-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A Novel Vaccination System Utilizing Protein-transduction Domain2007

    • Author(s)
      N. Shibagaki
    • Organizer
      World Congress of Dermatology
    • Place of Presentation
      Buenos Aires. (Argentine)
    • Year and Date
      2007-10-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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