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

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？×？109 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, VSVΔ51 combined with ZD6126 led to a significant increase in viral replication in these tumours.Our data suggest that the combinations of VSVΔ51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.Head and neck squamous cell carcinoma (HNSCC) is the most common cancer type in the head and neck region, accounting for the 5th most common cancer worldwide [1]. Locally advanced diseases are treated with either radiation or chemo-radiotherapy, but are still associated with >50% mortality rate [1,2], underscoring the need to develop novel therapeutic strategies. Oncolytic viruses have recently garnered increasing interest as anti-cancer agents due to their preferential killing of transformed cells (reviewed in [3,4]). Among these, the mutant variant of vesicular stomatitis virus (VSV) has been evaluated in different tumour models, demonstrating promising results as either single agent or in combination with other treatment modalities [5-7]. We had previously demonstrated the exquisite sensitivity of EBV-positive nasopharyngeal carcinoma (NPC) to a mutant VSV (VSVΔ51), which has a single amino acid deletion in the VSV M protein, rendering lethality to cancer cells, whilst sparing normal cells [8]. Building upon this observation, herein we evaluated the efficacy of VSVΔ51 against the human FaDu hypopharyngeal squamous cell carcinoma model either as a single agent, or combined with radiation therapy (RT) or the vascular disrupting agent ZD6126. ZD6126 is a colchicine pr