Cross-presentation of NY-ESO-1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells

Seiya Susumu, Yasuhiro Nagata, Shinichiro Ito, Mitsutoshi Matsuo, Danila Valmori, Katsuyuki Yui, Heiichiro Udono, Takashi Kanematsu

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The cancer-testis antigen NY-ESO-1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8+ T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen-presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen-processing pathway (cross-presentation). Therefore, we genetically fused a minigene encompassing the NY-ESO-1 cytotoxic T lymphocyte (CTL) epitope 157-165 (ESO p157-165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen-A*0201-restricted NY-ESO-1-specific CTL clone, the cross-presentation of ESO p157-165 by monocyte-derived dendritic cells (mo-DC) pulsed with the fusion protein was evaluated. The fusion protein-pulsed mo-DC activates the CTL clone much more efficiently than the free NY-ESO-1 protein-pulsed mo-DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157-165 and the fusion protein of hsc70 and ESO p157-165 (hsc70-ESO p157-165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo-DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70-ESO p157-165 fusion protein-pulsed DC was able to induce an antigen-specific T-cell response. These results suggest that the hsc70-ESO p157-165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalCancer Science
Volume99
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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