Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours

Hypoxia contributes to the aggressive and treatment-resistant phenotype of pancreatic ductal adenocarcinoma (PDAC). Oncolytic vaccinia virus has potential as an anti-tumour agent but the ability to lyse hypoxic tumour cells is vital for clinical efficacy. We hypothesised that unique aspects of the poxvirus lifecycle would protect it from attenuation in hypoxic conditions. We characterised and compared the viral protein production, viral replication, cytotoxicity and transgene expression of Lister strain vaccinia virus in a panel of pancreatic cancer cell lines after exposure to normoxic or hypoxic conditions. Viral protein production was not affected by hypoxia, and high viral titres were produced in both normoxic and hypoxic conditions. Interestingly there was a five-fold (P<0.001) and 10-fold (P<0.0001) increase in viral cytotoxicity for CFPac1 and MiaPaca2 cell lines respectively in hypoxic conditions. Cytotoxicity was equivalent in the remaining cell lines. Levels of transgene expression (luciferase reporter gene) from the vaccinia viral vector were comparable regardless of the ambient oxygen concentration. The present study suggests that vaccinia virus is a promising vector for targeting pancreatic cancer and potentially other hypoxic tumour types.