Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines

Oncolytic viruses (OVs) are promising anticancer treatments that specifically replicate in and kill cancer cells and have profound immunostimulatory effects. We previously reported the potential of vanadium-based compounds such as vanadyl sulfate (VS) as immunostimulatory enhancers of OV immunotherapy. These compounds, in conjunction with RNA-based OVs such as oncolytic vesicular stomatitis virus (VSV & UDelta;51), improve viral spread and oncolysis, leading to long-term antitumor immunity and prolonged survival in resistant tumor models. This effect is associated with a virus-induced antiviral type I IFN response shifting towards a type II IFN response in the presence of vanadium. Here, we investigated the systemic impact of VS+VSV & UDelta;51 combination therapy to understand the immunological mechanism of action leading to improved antitumor responses. VS+VSV & UDelta;51 combination therapy significantly increased the levels of IFN-gamma and IL-6, and improved tumor antigen-specific T-cell responses. Supported by immunological profiling and as a proof of concept for the design of more effective therapeutic regimens, we found that local delivery of IL-12 using VSV & UDelta;51 in combination with VS further improved therapeutic outcomes in a syngeneic CT26WT colon cancer model.