Herpes oncolytic therapy of salivary gland carcinomas

Abstract

Oncolytic herpes simplex viruses (HSV) have demonstrated potent antitumoral effects against a variety of human malignancies in preclinical studies and are in early clinical trials. We explored the activity of an attenuated, replication-competent, oncolytic HSV (NV1023) for the treatment of human salivary gland carcinomas. NV1023 was able to successfully enter into 4 mucoepidermoid carcinoma (H292, H3118, HTB-41, UT-MUC-1) and 2 adenocarcinoma (HSY, HSG) cell lines, as measured by lacZ assays after exposure to 5 viral particles per cell (MOI 5). Viral plaque assays showed variation of viral replication within these cell lines, ranging from a 268-fold increase (H292) to a 3-fold increase (HSG) in viral titer. At MOI 5, all cell lines showed >95% cytotoxicity from NV1023 by Day 7, except for HSY (73%). At MOI 0.1, H3118 and UT-MUC-1 remained highly sensitive to NV1023, both showing >95% cytotoxicity by Day 7. The mucoepidermoid carcinomas were more sensitive to NV1023 at low viral concentrations compared with the adenocarcinomas. Flank tumors of H3118, HTB-41 and HSY in nude mice showed significant tumor volume reductions after a single intratumoral injection of NV1023 (2 x 10(7) plaque-forming units). These data suggest that oncolytic herpes viruses have significant efficacy entering, replicating within, and lysing human salivary gland carcinomas. These promising biologic agents should be further investigated as novel therapy for patients with salivary carcinomas failing conventional treatment.