Oncolytic Reovirus as a Combined Anti-Viral and Anti-Tumour Agent for the Treatment of Liver Cancer

摘要

Objective: Oncolytic viruses (OVs) represent promising, pro-inflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit hepatitis C virus (HCV) whilst suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. Design & results: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity, and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of hepatitis B virus (HBV) associated HCC, as well as an alternative endogenous model of Epstein Barr Virus (EBV)-associated lymphoma. Interestingly, Reo appeared superior to the majority of OV in its ability to elicit innate inflammatory responses from primary liver tissue. Conclusions: We propose that Reo and other select pro-inflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-HCC, Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.