Tumor-derived heat shock protein chaperones tumor-antigenic peptides

Heat shock proteins (HSPs) facilitate intracellular translocation of antigenic peptides as chaperones and play an essential role in antigen processing and presentation. Tumor-derived HSPs function as tumor rejection antigens to induce tumor-specific transplantation resistance. To determine if tumor-derived HSPs chaperone tumor-antigenic peptides, we purified hsp70, gp96 and hsp90 from mouse radiation-induced leukemia RL ♂ 1 and dissociated peptides from the HSPs. Tandem mass spectrometry of the dissociated peptide fractions with which RL ♂ 1-specificity CTL, Y-15 exhibited cytotoxicity against peptide-pulsed P815 revealed that hsp70 was associated with a known tumor-rejection-antigenic peptide, pRL1a, gp96 was associated with pRL1 and its precursor peptide, pRL1b, and hsp90 was associated with pRL1, pRL1b and other unknown antigenic peptide. Hsp70 and gp96 purified from surgically resected human colon cancer strongly stimulated autologous peripheral blood mononuclear cells for the production of interferon γ, tumor necrosis factor α and proliferative responses. The cytotoxicity of tumor-specific cytotoxic T lymphocytes was also induced by the culture with the hsp70. These results suggest that the autologous cancer-derived HSP, which is associated with both known and unknown tumor-antigenic peptides, is an effective tumor vaccine for the immunotherapy of cancers without the HLA haplotype restriction.