Heat immunotherapy with heat shock protein expression by hyperthermia using magnetite nanoparticles

Hyperthermia is a possible approach for cancer therapy. However, a major technical problem associated with the use of hyperthermia is the difficulty of heating the local tumor region to the intended temperature without damaging normal tissue. Accordingly, in hyperthermia treatment, the expression of heat shock proteins (HSPs) has been considered a complicating factor because the expression of HSPs protects cells from apoptotic cell death. In cancer immunity, on the other hand, HSPs, including HSP70, have been shown to play an important role in immune reactions. If HSP expression induced by hyperthermia is involved in tumor immunity, novel cancer immunotherapy based on hyperthermia treatment can be developed. In such a strategy, a tumor-specific hyperthermia system that can induce necrotic cell death via HSP expression without damaging non-cancerous tissues would be highly advantageous. An intracellular hyperthermia system using functionalized magnetite nanoparticles, including magnetite cationic liposomes and antibody-conjugated magnetoliposomes, facilitates tumor-specific hyperthermia; this can induce necrotic cell death via HSP expression, which in turn induces antitumor immunity. We term this novel cancer therapy as "heat immunotherapy." This review discusses recent progress in cancer immunology via HSP expression and novel immunotherapy based on hyperthermia.