Combination of virotherapy with VSV and tumor vaccination significantly enhances the efficacy of antitumor therapy.

Abstract

Oncolytic virotherapy offers the potential to treat tumors both as asingle agent and in combination with conventional therapies such as chemotherapy and immunological therapy. Here, we describe an effective treatment regimen which combines virotherapy with immunotherapy. IFN-α and co-stimulator IL-2 along with tumor cell lysate vaccination with intratumoral administration of oncolytic vesicular stomatitis virus (VSV) resulted in regression of established TC1 papilloma tumor model in C57BL/6 mice. The remarkable results especially in the group receiving tumor vaccination and virotherapy together (TC1-VSV) were obtained. Combination therapy synergistically enhanced CTL activity against tumor cells and reduced tumor size, although significant reduction in tumor size was observed in both groups receiving VSV or tumor vaccine alone. The presented data suggest that the effectiveness of virotherapy is enhanced when combined with immunotherapy by priming specific CD8 Tcells against tumor antigens through tumor vaccination and boosting by exposure of antigens upon virus infection. Keywords: virotherapy; VSV; tumor vaccine; immunotherapy; IFN-α; IL-2.