HSP70-based anti-cancer immunotherapy

Heat shock protein 70, (Hsp70) constitutes a powerful system of cytoprotection in all organisms studied to date. Exerting such activity, Hsp70 rescues cancer cells from antitumor therapy, posing a great challenge for oncologists. In contrast to its protective action, Hsp70 was found to be released from cancer cells, prompting cytotoxic lymphocytes to target and kill the tumor. A great number of vaccines have been developed on the basis of the ability of Hsp70 to present tumor antigen or to elevate the sensitivity of cancer cells to cytotoxic lymphocytes. In this commentary, we consider novel data on the employment of pure Hsp70 in the therapy of glioma and melanoma malignancies. We show that intratumorally delivered Hsp70 penetrates cancer cells and pulls its intracellular analog outside of the cell. This displacement may activate cells, constituting both innate and adaptive immunity. In vivo delivery of Hsp70 was found to inhibit tumor growth and to extend survival. The technology of intratumoral injection of pure Hsp70 passed through preclinical trials and was investigated in clinics for children with brain cancer; the results show the safety and feasibility of a new approach.