Investigation of the oncolytic activity of vesicular stomatitis virus in murine cancer models

Interferon (IFN) inducing strains of Vesicular stomatitis virus (VSV) replicate selectively in transformed cells and exert impressive oncolytic abilities in murine tumour models. Interestingly, in some tumour models, complete tumour cures can only be obtained by administering multiple intravenous doses of virus, indicating that there must be barriers that limit the ability of a single dose of virus to eliminate a tumour. The goal of the current research was to examine the intravenous delivery of IFN inducing VSV to subcutaneous tumours, as well as subsequent spread and tumour killing activity. It was found that intravenous delivery is inefficient and seems to result in preferential delivery of virus to the tumour rim. However, apoptosis is induced throughout the uninfected core of the tumour, indicating that VSV may induce indirect killing of tumour cells. While the specific cause of this apparent bystander effect was not determined, it was observed that VSV treatment also resulted in collapse of functional tumour vasculature.