Oncolytic viruses represent one of the oldest classes of cancer therapeutics and are characterized by their preferential ability to replicate in and lyse cancer cells while sparing normal cells due to cancer cell-inherent defects in innate immune signaling. Despite the apparent selectivity for cancer cells, clinical efficacy of systemically-administered oncolytic viruses to date has been limited, while mechanisms of response and resistance to these agents remain poorly understood. In my talk, I will summarize our work focusing on understanding of the mechanisms of anti-tumor therapy elicited by oncolytic viruses using Newcastle Disease Virus (NDV) as a model. I will discuss the mechanistic basis underlying the activation of anti-tumor immune response by oncolytic viruses, mechanisms of adaptive immune resistance, and implications for using oncolytic viruses as potentiators of response to immune checkpoint blockade. I will further discuss how modulation of different features of oncolytic virus biology, including pre-existing immunity, viral replication, and genetic introduction of therapeutic transgenes can perturb the balance between the anti-viral and anti-tumor immunity, and lead to unexpected and sometimes undesired effects on therapeutic efficacy. Finally, I will highlight how these findings have been applied to human cancers, and will discuss our ongoing efforts to use oncolytic viruses as a strategy to overcome resistance to immunotherapy in ovarian cancer.
(Refreshments will be served at 2:15 pm)