Treating human cancers with heat shock protein-peptide complexes: the road ahead

Abstract

Background: Heat shock proteins (HSPs) chaperone a wide array of peptides generated in cells. Association of HSPs with peptides is critical for loading of MHC I with epitopes, and has been suggested to be essential for cross-presentation. HSP–peptide complexes purified from cancer cells have been shown to chaperone tumor-specific antigenic epitopes, and have been used in experimental immunotherapy of human cancers. Two randomized Phase III trials have been completed recently. Objective: To summarize the lessons learned from the Phase III studies and to opine on the path forward. Results/conclusion: Immunization of human subjects with HSP–peptide complexes derived from autologous tumors mediates substantial clinical benefit in subjects with relatively early stage disease, consistent with results seen in animal models of cancer, and with an immunological mechanism of action. Additional clinical studies are essential for further development of this personalized medicine.

Keywords::

• cross-presentation
• cross-priming
• dendritic cells
• glioblastoma
• gp96
• hsp70
• hsp90
• melanoma
• renal cell carcinoma
• subset analysis
• vitespen