Effective gene immunotherapy for melanoma utilizing an advanced in vivo electrotransfer system

Interleukin-12 (IL-12) is a potent immune stimulator that induces the proliferation and activation of natural killer (NK) and T cells and the secretion of interferon (IFN)-γ. While IL-12 is an effective anti-cancer therapy, high concentrations may produce unwanted adverse effects or result in immune suppression. We previously demonstrated that intratumor delivery of a plasmid encoding IL-12 with gene electrotransfer (GET) induced local and systemic tumor control with no detected adverse effects. However, the shortcomings of standard GET are that high voltage is required and the lack of a delivery completion signal. We recently developed an improved system that overcomes these issues by incorporating sophisticated electrodes, mild heat application, and real time tissue impedance monitoring. In this study, we validated this advanced electrotransfer system. We compared the therapeutic efficacy of intratumor IL-12 GET in B16-f10 mouse melanomas delivered by standard and advanced technologies. Delivery with both standard and advanced electrotransfer reduced the tumor specific growth rate and increased survival. Our results demonstrated that therapeutic in vivo gene delivery can be achieved with a less intense pulse regimen.