Oncolytic vaccinia virus therapy of salivary gland carcinoma.

Salivary gland carcinomas are relatively rare malignant tumors, accounting for less than 5% of all cancers of the head and neck.1 They encompass a wide spectrum of histologic abnormalities with varied biologic behavior. Initial therapy of localized disease consists of complete surgical excision. The risk of recurrence and metastasis is significantly higher in patients with locally advanced salivary carcinomas. Individuals with high-grade salivary carcinomas have a 5-year survival of roughly 40%; those with low-and intermediate-grade tumors have a 5-year survival of 85% to 90%.2,3 For these patients, complete surgical resection followed by postoperative radiation therapy is recommended.4 Unfortunately, patients with recurrent and/or unresectable disease have few effective treatment options. Clinical trials exploring the role of chemotherapy in the management of salivary gland carcinomas failed to show survival benefit.1 Chemotherapy, therefore, is generally reserved as a palliative measure for patients with symptoms and/or rapid disease progression. Clearly, novel therapies are needed to improve outcomes for patients with salivary carcinomas. Oncolytic viruses have emerged as versatile therapeutic agents that can selectively infect, replicate within, and ultimately lyse a host cancer cell. A variety of viruses have been reported5–7 to possess on-colytic antitumoral activity, including herpes simplex type 1, adenovirus, reovirus, vesicular stomatitis virus, measles virus, poliovirus, West Nile virus, and New-castle disease virus. Vaccinia virus, which is a double-stranded DNA member of the genus Orthopoxvirus, has many unique characteristics that make it an excellent tool in cancer treatment. In addition to its natural tropism for tumor tissues and its abilities for efficient entry, replication, and lysis, vaccinia virus has a remarkable safety record in its historical widespread human application as a vaccine for smallpox. The vaccinia replication cycle occurs exclusively in the cytoplasm, which eliminates the possibility of chromosomal integration.7 Furthermore, there are many Food and Drug Administration–approved antiviral agents available to limit viral spread and control the unlikely possibility of viral toxicity.8 Consequently, several recombinant vaccinia viruses have been constructed and studied in preclinical and clinical phase 1 settings.8,9 Recombinant, replication-competent vaccinia virus (GLV-1h68) has been reported10–16 as effective in breast cancer, thyroid cancer, mesothelioma, pancreatic cancer, prostate cancer, human hepatocellular carcinoma, and head and neck cancer models. The aim of this study was to assess the usefulness of GLV-1h68 as a therapeutic agent against salivary gland carcinoma in vitro and in vivo. Murine flank and orthotopic parotid tumor models were used.