Enhanced vesicular stomatitis virus (VSVΔ51) targeting of head and neck cancer in combination with radiation therapy or ZD6126 vascular disrupting agent

Background: Head and neck squamous cell carcinoma (HNSCC) is the 5th most common cancer worldwide. Locally advanced HNSCC are treated with either radiation or chemo-radiotherapy, but still associated with high mortality rate, underscoring the need to develop novel therapies. Oncolytic viruses have been garnering increasing interest as anti-cancer agents due to their preferential killing of transformed cells. In this study, we evaluated the therapeutic potential of mutant vesicular stomatitis virus (VSV Delta 51) against the human hypopharyngeal FaDu tumour model in vitro and in vivo. Results: Our data demonstrated high toxicity of the virus against FaDu cells in vitro, which was associated with induction of apoptosis. In vivo, systemic injection of 1 x 10(9) pfu had minimal effect on tumour growth; however, when combined with two doses of ionizing radiation (IR; 5 Gy each) or a single injection of the vascular disrupting agent (ZD6126), the virus exhibited profound suppression of tumour growth, which translated to a prolonged survival in the treated mice. Concordantly, VSV Delta 51 combined with ZD6126 led to a significant increase in viral replication in these tumours. Conclusions: Our data suggest that the combinations of VSV Delta 51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.