Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Recent Progress and Emerging Trends

Oncolytic virotherapy has emerged as a promising and innovative approach to cancer treatment, leveraging viruses that selectively replicate in tumor cells and cause their destruction (oncolysis), while simultaneously stimulating anti-tumor immune responses. Vesicular stomatitis virus (VSV), a prototypic rhabdovirus, is among the most versatile oncolytic virus platforms due to its favorable biological characteristics, including rapid replication and cell lysis, lack of pre-existing immunity in humans, and amenability to genetic engineering. Over the past decade, significant progress has been made in VSV-based oncolytic virotherapy. This review presents a comprehensive update on developments since our last review, emphasizing improvements in VSV safety, oncoselectivity, tumor-specific replication, direct oncolysis, and induction of antitumor immunity. By integrating recent applied discoveries with foundational knowledge, this review aims to guide ongoing efforts to advance VSV-based oncolytic virotherapy toward broader clinical translation and improved cancer patient outcomes. Additionally, we provide an overview of three closely related rhabdoviruses (Maraba, Morreton, and Jurona viruses) as emerging oncolytic platforms currently under preclinical and clinical investigation.