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01.12.2012 | Primary research | Ausgabe 1/2012 Open Access

Cancer Cell International 1/2012

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

Zeitschrift:
Cancer Cell International > Ausgabe 1/2012
Autoren:
Nehad M Alajez, Joseph D Mocanu, Tiffany Krushel, John C Bell, Fei-Fei Liu
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2867-12-27) contains supplementary material, which is available to authorized users.

Competing interests

There are no competing interests.

Authors’ contributions

NMA designed and did the experiments and wrote the manuscript; JDM helped with sample processing and microscopy, TK helped with proliferation and apoptosis experiments, JCB provided VSVΔ51 virus, and FFL conceived the study and obtained funding.All authors read and approved the final manuscript.

Abstract

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 (VSVΔ51) 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 × 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.

Conclusions

Our data suggest that the combinations of VSVΔ51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Literatur
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