Hyperthermia-regulated immunogene therapy

One of the key milestones that must be reached before gene therapy becomes feasible for clinical cancer treatment is to be able to regulate therapeutic gene expression. This is true for most current cancer gene therapy approaches, since the majority of therapeutic genes are toxic to both tumour and normal tissues. Among the wide array of strategies available for regulating gene expression, hyperthermia represents a unique approach. Hyperthermic regulation of gene therapy is feasible because of the widely conserved heat shock response, which allows therapeutic gene expression to be elevated to thousands of fold higher than background when temperature reaches 3-5 degrees C over physiological temperature (37 degrees C). In addition, because of the long history of experimental research on the use of hyperthermia as an approach for cancer therapy, it is now quite feasible to apply hyperthermia to a number of tumour sites and to achieve temperatures that are sufficient to induce a heat shock response. This review will attempt to discuss the current status of hyperthermia-regulated gene therapy, with special emphasis on hyperthermia-regulated immunogene therapy.