Oncolytic vaccinia virus as a precision cancer vaccine platform

Oncolytic viruses (OVs) are a unique immunotherapeutic tool as they possess the ability to selectively replicate in and kill tumor cells while also having the potential to induce potent anti-tumor immune responses. Further, the use of OVs as payload delivery systems to the tumor offers a precision approach to enhancing immune responses generated during OV therapy through the viral expression of immune stimulating molecules in the tumor. Notably, Vaccinia virus (VACV) is a strong oncolytic candidate due to its ability to infect a wide range of cancer cells, and a genome capable of harbouring large inserts of exogenous DNA. Peptide-Major Histocompatibility Complexes (pMHC-I) are vital components of the immune recognition of tumors, leading to the activation of antigen specific T cells and targeted killing of cells. Here, we examined the use of an oncolytic VACV (VACVΔ4x) expressing a single chain trimer (SCT) pMHC-I complex (VACVΔ4x-SCT) encoding a tumor associated or specific antigen. VACVΔ4x-SCT treatment was investigated in two immunologically cold tumor models, B16F10 melanoma and EMT6 breast cancer. VACV expression of tumor specific SCTs lead to drastic differences in tumor growth between the two models, where enhanced tumor clearance was observed in the EMT6 model. Tumor antigen specific CD8+ T cells were isolated from both tumor and spleen following VACV-SCT treatment, indicating the ability to induce targeted tumor specific responses with viral therapy. Initial tumor clearance was also observed to be protective in the EMT6 model, leading to tumor rejection upon subsequent challenge. Overall, we demonstrate the ability to generate a personalized cancer vaccine capable of inducing system recognition and elimination of tumor cells, validating VACV as a potential vaccine platform.