Oncolytic Measles Virus Encoding Interleukin-12 Mediated Antitumor Activity and Immunologic Control of Colon Cancer In Vivo and Ex Vivo

Background: In this study, we used an oncolytic measles virus encoding interleukin 12 (IL-12) to treat colon cancer in vivo and ex vivo to investigate its effect on the viability and apoptosis of colon cancer cells. Method: A rat model was established to evaluate the immunostimulatory capabilities and therapeutic efficacy of vectors encoding an IL-12 fusion protein (MeVac FmIL-12 vectors). TUNEL staining, western blot, and enzyme-linked immunosorbent assay were performed to examine the impacts of MeVac FmIL-12 on the expression of inflammatory cytokines. Cell transfection was carried out to validate the anti-tumor role of MeVac FmIL-12 in vitro. Flow cytometry and MTT assay were performed to assess the effects of MeVac FmIL-12 on cell apoptosis and viability. Result: High concentrations (10-1000 ng/mL) of murine IL-12 fusion protein (FmIL-12) decreased the production of interferon gamma (IFN-gamma) in a concentration-dependent manner and reflected FmIL-12-induced overstimulation. Rats treated with MeVac vectors encoding FmIL-12 showed a significantly increased level of FmIL-12 overtime and a concentration-dependent (0.01-10 ng/mL) increase in IFN-gamma production. MeVac FmIL-12 also increased the expression of inflammatory cytokines (IFN-gamma, tumor necrosis factor alpha, and IL-6) both in vivo and in vitro. MeVac FmIL-12 promoted cell apoptosis and reduced cell viability, which helped to trigger a systemic anti-tumor immune response, both in vivo and in vitro. Conclusion: In this study, we suggested that MeVac FmIL-12 enhanced the therapeutic efficacy of tumor treatment by improving anti-tumor immunity.