ORIGINAL ARTICLE Edward J. Shin, MD, Jaime I. Chang, MD, Bryan Choi, MS, Georges Wanna, MD, Oliver Ebert, MD, Eric M. Genden, MD, and Savio L.C. Woo, PhD, New York, NY Otaryngology-Head and Neck Surgery (2007) 136, 811-817 Fusogenic vesicular stomatitis virus for the treatment of head and neck squamous carcinomas From the Departments of Otolaryngology-Head and Neck Surgery ( Drs Shin, Chang, Mr Choi, Drs Wanna, Genden) and Gene and Cell Medicine (Drs Ebert and Woo), Mount Sinai School of Medicine. Presented at the Annual Meeting of the American Academy of Otolar- Yngology-Head and Neck Surgery, Los Angeles, CA, September 25-28, 2005. Reprint requests: Edward J. Shin, MD, Mount Sinai School of Medi- cine, One Gustave L. Levy Place, Box 1189, New York, NY 10029. E-mail address: entshin@yahoo.com . 0194-5998/$32.00 © 2007 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. doi:10.1016/j.otohns.2006.11.046 Objectives: This study investigates the efficacy of recom- binant fusogenic VSV [rVSV-NDV/F(L289A) or rVSV-F] in the treatment of head and neck squamous cell carcinoma. (HNSCC). Study and Design Setting: The vitro replication and cytotoxicity of rVSV-F were studied in two human SCC cell lines, in one murine SCC cell line, and in human kertino- cytes. The effects on tumor size and animal survival were investigated following in vivo rVSV-F treatment of floor-of- mouth tumor model C3H/HeJ mice. Results: Recombinant VSV-F preferentially induced rapid syncytia formation, and replicated in (p < 0.04) and killed (P< 1 X 10 ) all three SCC lines tested. The virus had no observable effect on human keratinocytes. Tumor size was smaller ( P < 0.03) and overall survival was better (P < 0.001) for treated animals than for control animals. Conclusion / Significance: Recombinant VSV-F confers a modest survival benefit for HNSCC in this orthotopic murine model. This oncolytic virus holds promise as a novel cancer treatment for recurrent HNSCC. ©2007 American Academy of Otolaryngology - Head and Neck Surgery Foundation. All rights reserved. Head and neck cancer has an estimated yearly incidence of 38,530, with 11,060 associated moralities. As many as 33% of treated patients develop recurrent disease. -13 The treatment of these patients is a challenge because of their poor prognosis, despite the options of salvage surgery and / or re-irradiation (with or without chemo- therapy). One prospective study has shown that surgical salvage of resec- table disease gives a median disease-free survival interval of 17.9 months, with an overall two-year disease free survival rate of 44%. Unfortunately, most patients present with unresectable disease, in which case the chances of survival are even more dismal. Systemic chemotherapy, is an option for carefully selected patients but gives only slightly better results. Given these unsatis- factory results, new treatments are ugently required for patients with recurrent head and neck cancer. A novel approach is the use of oncolytic viruses. Vesicular stomatitis virus (VSV) has demonstrated potency as an oncolytic virus in preclinical tumor models of glioma, hepatocelluar carcinoma, breast carcinoma, and mela- noma. By taking advantage of the inherent attenuated antiviral responses of tumor cells, viruses, such as VSV, can be development of more virulent oncolytic viruses with shorter replication cycles is required. Ebert et al (2004) have generated a fusogenic VSV with enhanced oncolytic potential for the treatment of hepato- celular carcinoma. In this modification, VSV is genetically engineered to incorporate the sequence that codes for a mutated Newcastle disease virus (NDV) protein, NDV - F(L289A), to form rVSV - NDV/F (L289A), which is capable www.ent-newyork.com