Tumour cells possess many features which predispose them to viral infections, including an abundance of replication resources, a defective interferon response and localised evasion of host immune cells. Oncolytic viruses take advantage of these characteristics in order to preferentially replicate within tumour cells, undergoing unchecked replication and targeting cells for destruction by the host immune system. Vaccinia virus (VACV) is a well characterised oncolytic agent, which has previously been studied in the context of its role in the smallpox vaccine. However, the new generation immunotherapeutic strain, JX-594, contains many genetic modifications which distinguish it from the parental strain. For example, a deletion of B18R raises the susceptibility of the virus to interferons, allowing healthy cells to rapidly clear infection. While various modes of delivery of JX-594 have been trialled, currently the most effective route is intratumoral injection. Unfortunately, this can hold the risk of dislodging malignant cells, allowing them to intravasate and form distal tumours. We propose that promoting VACV-induced cell invasion could improve the efficacy of intravenous delivery, and in turn decrease the risk of secondary tumour formation. Our lab has observed that many properties of infected cells favour an invasive phenotype, including high levels of cell migration, loss of cell polarity and invasion during gelatin assays. As cell invasion is often facilitated by matrix metalloproteinases (MMPs), we studied their role during infection, and found degradation of the extracellular matrix to be dependent on a number of these proteins. Furthermore, various regulators of the cytoskeleton and MMPs can be detected by qPCR and immunoblot following virus addition. This work suggests combination therapy with JX-594 and MMP inhibitors could have a synergistic effect on the treatment of invasive cancers, by limiting MMP-mediated invasion of cancer cells, and allowing VACV to target any remaining drug-resistant tumour cells.