Oncolytic viruses have gained much attention in recent years, due, not only to their ability to selectively replicate in and lyse
tumor cells, but to their potential to stimulate antitumor immune responses directed against the
tumor.
Vesicular stomatitis virus (VSV), a negative-strand RNA virus, is under intense development as an oncolytic virus due to a variety of favorable properties, including its rapid replication kinetics, inherent
tumor specificity, and its potential to elicit a broad range of immunomodulatory responses to break immune tolerance in the tumor microenvironment. Based on this powerful platform, a multitude of strategies have been applied to further improve the immune-stimulating potential of VSV and synergize these responses with the direct oncolytic effect. These strategies include: 1. modification of endogenous virus genes to stimulate
interferon induction; 2. virus-mediated expression of
cytokines or immune-stimulatory molecules to enhance anti-
tumor immune responses; 3. vaccination approaches to stimulate adaptive immune responses against a
tumor antigen; 4. combination with adoptive immune
cell therapy for potentially synergistic therapeutic responses. A summary of these approaches will be presented in this review.