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2003 Fiscal Year Final Research Report Summary

Application of Heat-shock protein with antigenic peptide for cancer vaccine

Research Project

Project/Area Number 14571146
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, 助手 (80336164)

Co-Investigator(Kenkyū-buntansha) 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)
UDONO Heiichiro  Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (50260659)
Project Period (FY) 2002 – 2003
KeywordsHeat-shock protein / Cancer Vaccine / NY-ESO-I / 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-I, 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-l epitope fusion protein.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Nagata Y, Ono S, 他: "Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1,by distinct human dendritic cell populations."Proc Natl Acad Sci USA. 99・16. 10629-10643 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gnjatic S, Hike J, 他: "CD8(+) T cell responses against a dominant cryptic HLA-A2 epitope after NY-ESO-1 peptide immunization of cancer patients."Proc Natl Acad Sci USA. 99・18. 11813-11818 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamano T, Murata S, 他: "Two distinct pathways mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing."J Exp Med.. 196・2. 185-196 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tominaga N, Ohkusu-Tsukada K, 他: "Development of Th1 and Th2 immune responses in mice lacking interferon regulatory factor-4."Int.Immunol.. 15. 1-10 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Udono H, Saito T, 他: "Hsp-antigen fusion and their use for immunization."Methods.. 32・1. 21-24 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata Y, et al.: "Differential presentation of a soluble exogenous tumor antigen, NY ESO-l, by distinct human dendritic cell nonulations."Proc Natl Acad Sci USA. 99(16). 10629-10634 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gnjatic S, et al.: "CD8(+) T cell responses against a dominant cryptc 1-ILA-A2 epitope after NY ESO-1 peptide immunization of cancer patients."Proc Natl Acad Sci USA. 99(18). 11813-11818 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamano T, et al.: "Two distinct pathway mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing."J.ExMed.. 196. 185-196 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tominaga N, et al.: "Development of Th1 and Th2 immune responses in mice lacking interferon regulatory factor-4."Int.Immuuol.. 15. 1-10 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Udono H, et al.: "Hsp-antigen fusion and their use for immunization."Methods.. June 32(1). 21-24 (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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