Immunomodulating activity of mycobacterial heat shock protein 65 in tumor cells

In recent years, heat shock proteins have been shown to be effective in enh ancing the immunogenicity of tumors. In this study, we examined the effect of mycobacterial hsp65 gene transfection in a nonimmunogenic and aggressive tumor cell-line in order to understand the factors that could contribute t o the increase in immunogenicity mediated by Hsp65. The transfected cells w ere found to have indeed lost their tumorigenenicity and increased their im munogenicity. Tumor-specific cytotoxic T cells were present only in mice im munized with the Hsp65-expressing cells. Furthermore, endogenous Hsp70 was significantly increased in irradiated Hsp65-expressing cells and recombinan t Hsp65 protein was able to stimulate the mRNA expression of various T help er I (Th1) and pro-inflammatory cytokines in splenocyte cultures, as well a s a modest expansion of CD4 T cells. These results provide further evidence of the immunomodulating properties of Hsp65, which could be exploited for the treatment of cancer.