Multimodal immune activation abilities and characteristics of reovirus.

Reovirus is a ubiquitous, non-pathogenic, double stranded RNA virus with anti-tumor properties. The virus's replicative potential is regulated by phosphorylation of protein kinase receptor (PKR). In cancers with RAS pathway activation which leads to dysregulation of PKR, the virus maintains its protein translational potential and induces oncolysis. Systemic chemotherapy remains the standard of care for metastatic colorectal cancer with the addition of biologic agents in KRAS wildtype subtypes. In KRAS mutant colorectal cancers, there has been no added benefit to biologic agents. The therapeutic potential of reovirus (Reolysin®, pelareorep, Oncolytic Inc., Calgary, Canada), which induces its oncolysis with RAS activation through multimodal immune mechanisms, has been demonstrated in preclinical and clinical studies. In this review, we outline the specific immune mechanisms of reovirus induced oncolysis and provide both preclinical and clinical data on its applications in metastatic colorectal cancer patients. AJTR