Latest insights into oncolytic viro-immunotherapy with vesicular stomatitis virus

Vesicular stomatitis virus (VSV), a rhabdovirus with intrinsic oncolytic properties, has emerged as a promising candidate for cancer therapy. Thanks to impaired antiviral responses affecting cancer cells, particularly downregulated type I interferon signaling, VSV selectively replicates in tumor cells while sparing normal cells. To mitigate neurotoxicity and improve therapeutic efficacy, genetically-engineered strains, such as VSV-∆M51, VSV-mIFNβ, and VSV-GP, have been developed. This review highlights the latest advances in VSV-based oncolytic virotherapy, focusing on novel modifications of the viral genome, as well as on combination strategies designed to enhance tumor selectivity, stimulate antitumor responses, and overcome resistance mechanisms. Recent studies have introduced modifications that bolster immunogenicity, and improve viral replication within tumors. Additionally, approaches combining VSV with small molecules, immune checkpoint inhibitors and other immunomodulatory agents, promise to augment antitumor activity. Emerging evidence suggests that VSV can reshape the tumor microenvironment, thus promoting robust adaptive antitumor immune responses. Ongoing research continues to explore strategies for improving systemic delivery, minimizing off-target effects, and enhancing viral persistence within the tumor bed. Further investigation and clinical translation will determine the full potential of VSV-based viroimmunotherapy in cancer treatment.