Oncolytic vaccinia virus expression of a defined peptide-MHCI complex as a precision cancer immunotherapy platform

Abstract

Oncolytic viruses are immunotherapeutic agents that selectively replicate in and kill tumour cells with the goal of promoting anti-cancer immune responses. Vaccinia virus (VACV) is a strong oncolytic virus candidate as it infects a wide range of cancer cells, is amenable to genetic tailoring and induces potent, long-lasting immunity. Here, we examine the use of genetically engineered oncolytic VACVs (oVACV) to express a variety of MHC-I complexes and the co-stimulatory ligand CD80 to stimulate anti-tumour CD8+ T cell responses in two syngeneic cancer models. Tumour antigen specific CD8+ T cells were detected in both the tumour and spleen following oVACV treatment, demonstrating the ability to induce tumour targeted T cell responses with viral therapy. oVACV expression of peptide-MHC-I complexes enhanced the efficacy of primary tumour clearance with tumour specific antigen targeting showing the greatest efficacy. Initial tumour clearance following treatment with oVACVs led to variable anti-tumour immune memory depending on the tumour model. Depletion of CD8+ T cells prevented therapeutic efficacy of oVACV while combination with PD-L1 immune checkpoint blockade enhanced tumour clearance. Overall, we demonstrate the ability to generate an oncolytic virus capable of inducing recognition and elimination of tumour cells through VACV-mediated expression of defined peptide-MHC-I complexes.