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)-gamma, 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-gamma 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-gamma. 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.
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)-gamma, 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-gamma 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-gamma. 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.
Authors: Khue G Nguyen; Maura R Vrabel; Siena M Mantooth; Jared J Hopkins; Ethan S Wagner; Taylor A Gabaldon; David A Zaharoff Journal: Front Immunol Date: 2020-10-15 Impact factor: 7.561