Gene electrotransfer of plasmids encoding cytokines as an effective immunotherapy approach for melanoma

Gene electrotransfer (GET) of plasmids encoding cytokines has been shown to generate a potent anti-tumor effect. Effective protocols have been developed delivering the plasmids directly into tumors. To obtain an effective immune response, it is critical to achieve a balance between transgene expression and tissue damage. GET is a reliable and effective physical method for in vivo delivery of plasmid DNA. It is particularly attractive for use in anti-cancer cytokine therapy as it does not incur the side effects associated with conventional protein cytokine therapy. Delivery of plasmids encoding cytokines directly to tumors has been shown by our lab and others to induce not only local immune response, but a systemic one as well. The positive responses were directly related to the ability to achieve the appropriate expression profile following delivery of the plasmid. Interestingly, the electrotransfer parameters were dependent on which cytokine was being delivered. For plasmid encoding IL-12 the correct parameters were 1300 V/cm and 100 us. For IL-15, the appropriate parameters were 600 V/cm and 5 ms. The procedure included injecting the plasmid DNA into established B16.F10 melanoma tumors of C57BL/6 mice and electric pulses applied three times over a one week period. To enhance this immune response, current work is further analyzing the immune response to determine if there is a marker that would indicate appropriate delivery of the plasmid. In addition, combination therapies are being explored to evaluate if the response could be augmented. A more complete understanding of the process and identifying other agents that could further augment this approach would be an important step.