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Enhancement of anti cancer immunity by fusion protein of HSP70 and CD8 T cell epitope from NY-ESO-1

Research Project

Project/Area Number 16591263
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNagasaki University

Principal Investigator

NAGATA Yasuhiro  Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (80336164)

Co-Investigator(Kenkyū-buntansha) UDONO Heiichiro  RIKEN YOKOHAMA INSTITUTE, Research Center for Allergy & Immunology, Team Leader, 横浜研究所, チームリーダー (50260659)
KANEMATSU Takashi  Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (40128004)
松尾 光敏  長崎大学, 医学部・歯学部附属病院, 助手 (00380840)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsHeat-shock protein / Cancer Vaccine / NY-ESO-1 / Dendritic Cell
Research Abstract

Heat shock proteins(HSPs) 70 are a family of highly conserved molecules with ATPase activity and relative molecular masses around 70,000 kDa. Hsp proteins chaperone antigenic peptides into antigen-presenting cells, potentially allowing peptides to enter the MHC class I pathway for loading onto MHC class I molecules, where they can be presented to cytotoxic CD8+ T cells. In turn, this provides a strategy for immunization against cancer by using hsp and bound peptides that are isolated from tumors. Immunization with heat shock cognate protein 70 (hsc70) bound to synthetic peptides by in vitro reconstitution has been shown to induce peptide-specific CTL in mice. Here, we succeed genetically to fuse hsc70 and a CTL epitope derived from NY-ESO-1, one of the cancer-testis antigens. We also have shown dendritic cell can present the epitope onto their MHC class I after feeding the fusion protein. Hsc70 with NY-ESO-1 peptide can be processed through cytosolic pathway and presented by DCs to CD8^+ T cell clones. These findings help devising and validating vaccine strategies with Hsc-NY-ESO-1 epitope fusion protein.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004

All Journal Article (12 results)

  • [Journal Article] Interferon regulatory factor-4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS.2005

    • Author(s)
      Honma, K., Udono, H.et al.
    • Journal Title

      Proc. Nat1 Acad. Sci. USA. 102(44)

      Pages: 16001-16006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interferon regulatory factor-4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS.2005

    • Author(s)
      Honma, K., Udono, H., et al.
    • Journal Title

      Proc Natl Acad Sci USA. 102(44)

      Pages: 16001-16006

    • Related Report
      2005 Annual Research Report
  • [Journal Article] IFN-γ enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation.2004

    • Author(s)
      Matsuo M., Nagata Y.et al.
    • Journal Title

      Proc Natl Acad Sci. USA 101(40)

      Pages: 14467-14472

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hsp-antigen fusion and their use for immunization.2004

    • Author(s)
      Udono, H., Saito, T.et al.
    • Journal Title

      Methods. 32

      Pages: 21-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine. Contamination with bacterialouter membrane proteins.2004

    • Author(s)
      Furukawa, H., Udono, H.et al.
    • Journal Title

      J. Biol. Chem. 279(22)

      Pages: 23661-23667

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of the Maintenance of Peripheral T-Cell Anergy by TAB1-Mediated p38 Activation.2004

    • Author(s)
      Ohkusu-Tsukada, K., Udono, H.et al.
    • Journal Title

      Mol. Cell. Biol. 24

      Pages: 6957-6966

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IFN-genables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation.2004

    • Author(s)
      Matsuo M, Nagata Y, Sato E, Atanackvic D, Valmori D, Chen YT, Ritter G, Mallman I, Old LJ, Gnjatic S.
    • Journal Title

      Proc Natl Acad Sci USA 101(40)

      Pages: 14467-14472

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hsp-antigen fusion and their use for immunization.2004

    • Author(s)
      Udono, H., Saito, T., Ogawa, M., Yui, K.
    • Journal Title

      Methods. 32

      Pages: 21-24

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine. Contamination with bacterialouter membrane proteins.2004

    • Author(s)
      Furukawa, H., Doh-ura, K., Okuwaki, R., Shirabe, S., Yamamoto, K., Udono, H., Ito, T., Katamine, S., Niwa, M.
    • Journal Title

      J.Biol.Chem. Vol.279, 22

      Pages: 23661-23667

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of the Maintenance of Peripheral T-Cell Anergy by TAB1-Mediated p38 Activation.2004

    • Author(s)
      Ohkusu-Tsukada, K., Tominaga, N., Udono, H., Yui, K.
    • Journal Title

      Mol.Cell.Biol. Vol.24

      Pages: 6957-6966

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interferon regulatory factor-4 negatively regulates the production of proiniammatory cytokines by macrophages in response to LPS.2004

    • Author(s)
      Honma, K, Udono, H., Kohno, T., Yamamoto, K., Ogawa, A., Takemori, T., Kumatori, A., Suzuki, S., Matsuyama, T, Yui, K.
    • Journal Title

      J.Biol.Chem. Vol.279, 22

      Pages: 23661-23667

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IFN-γ enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation.2004

    • Author(s)
      Matsuo M., Nagata Y.et al.
    • Journal Title

      Proc Natl Acad Sci USA. 101(40)

      Pages: 14467-14472

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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