Oncolytic VSV-IL-2 has enhanced anticancer vaccination adjuvant abilities.

BACKGROUND: Heterologous oncolytic virus prime-boost vaccination is emerging as a promising cancer immunotherapy to establish potent antitumor immunity. With their natural ability to specifically destroy cancer cells, oncolytic viruses also allow for direct oncolysis and our team has previously demonstrated that they can be used as vaccination adjuvants when co-administered with antigenic peptides. As such, adjuvant oncolytic virus vaccines can easily be tailored to target any antigen, which is particularly important in the context of personalized vaccines against patient-specific mutations. Here, we tested if oncolytic viruses engineered to express the immune-stimulating transgene interleukin-2 have improved vaccination adjuvant potential. METHODS: For this proof-of-concept study, we generated an oncolytic vesicular stomatitis virus (VSV) variant (MD51) that encodes the T-cell activator cytokine interleukin-2 and measured its vaccination adjuvant potential in a heterologous virus immune boosting approach, 1 week after immune priming compared with the parental virus (also MD51). Tumor-free and B16F10-Ova tumor-bearing mice were vaccinated against the Ova peptide using either virus as adjuvants. The immune response induced by each vaccination regimen was assessed by flow cytometry to characterize antigen-specific CD8 T cells over time. Treatment efficacy was also measured. RESULTS: Our data show that VSV-interleukin-2 is superior as a vaccine boosting adjuvant compared with the parental virus as it induces more antigen-specific CD8 T cells with enhanced effector functions that persist over time. VSV-interleukin-2 vaccination also improves tumor control and survival. CONCLUSIONS: Overall, we show that engineered oncolytic virus platforms, such as VSV-interleukin-2, have the potential to improve vaccination efficacy and treatment outcomes. Our findings deepen our understanding of the immune mechanisms underlying the use of oncolytic viruses as anticancer vaccination platforms and will allow for the development of a new generation of improved oncolytic virus vaccine adjuvants. TRIAL REGISTRATION NUMBER: NCT02285816.