In this study, we present a novel therapeutic approach for colorectal cancer by integrating oncolytic virotherapy with a peptide-based immune checkpoint inhibitor. We previously engineered a synthetic chimeric virus (VMG) that expresses the glycoprotein (G) from Morreton virus (MorV) while retaining the structural genes from vesicular stomatitis virus (VSV). Additionally, a 12-amino acid linear peptide, identified through phage display biopanning, was found to inhibit the CD47/SIRPĪ± interaction, thereby enhancing macrophage-mediated phagocytosis of tumor cells. The antitumor efficacy of this combination therapy was evaluated in two syngeneic mouse models, CT26 and MC38. Our findings demonstrate that the combined treatment significantly prolonged survival and delayed tumor growth in both CT26 and MC38 tumor-bearing mice.
Learning Objectives:
Upon completion, participant will be able to describe the engineering process and components of the synthetic chimeric virus (VMG).
Upon completion, participant will be able to explain the synergistic effects of the combination of oncolytic virotherapy and anti-CD47 peptide.
Upon completion, participant will be able to explore the engineering of VMG virus to express anti-CD47 peptide in the tumor microenvironment.
