Synergistic therapy by combination of a plant virus immunomodulator and IL-12 against murine ovarian cancer

Cowpea Mosaic Virus (CPMV) is an immunostimulatory agent that can induce antitumor immunity by reversing the immunosuppressive tumor microenvironment (TME) upon intratumoral treatment. In situ injection of CPMV activates and recruits innate immune cells which initiate tumor cell killing and antigen processing, ultimately launching systemic and adaptive antitumoral immunity. IL-12 is a promising proinflammatory cytokine that facilitates antigen processing and promotes T cell proliferation. CPMV primarily activates innate immune cells while IL-12 plays a key role in the adaptive immune response; therefore, we hypothesized that the synergistic combination of CPMV and IL-12 would be beneficial for reducing tumor burden. We tested our study using a murine ovarian carcinoma model. Mice were inoculated with bioluminescent tumor cells. Tumor burden was monitored using bioluminescence, body weight, and circumference. Survival was established based on humane endpoints. Our data show that the combination of CPMV + IL-12 outperforms the single-arm treatment. Robust efficacy is demonstrated for the combination group. In ongoing studies, we are deciphering the mechanism of action through immunological investigation. This work was funded in part through grants from NIH: R01 CA224505 and R01 CA274640.