Combination of IL-12 and IL-18 of electro-gene therapy synergistically inhibits tumor growth

Background: We previously showed that IL-12 electro-gene therapy (EGT) induces significant antitumor immunity. However, because interleukin (IL)-18 acts synergistically with IL-12 to augment Th1 responses and interferon (IFN)-γ, we designed an EGT protocol using IL-12+IL-18 with the aim of enhancing the antitumor effects obtained with IL-12 alone. Materials and Methods: Expression plasmids harboring the gene for IL-12 or IL-18 were cotransferred to subcutaneous murine CT26 tumors. Subsequent expression of IFN-y and the presence of CD8+ T cells within treated tumors were analyzed by semiquantitative RT-PCR. Results: IL-12+IL-18 EGT inhibited tumor growth significantly better than IL-12 EGT, which was consistent with significantly higher intratumoral levels of IFN-y. Enhanced infiltration of tumor tissues by CD8+ T cells was confirmed with both IL-12 and IL-12+IL-18 EGT. Finally, IL-12+IL-18 EGT, but not IL-12 EGT, significantly suppressed untreated contralateral tumors. Conclusion: EGT with IL-12 and IL-18 is potentially an effective antitumor gene therapy.