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

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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.