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Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Herpes oncolytic therapy of salivary gland carcinomas
Vincent Reid1, Zhenkun Yu, Theodore Schuman
1Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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.
Insights
Oncolytic herpes simplex virus (HSV) NV1023 effectively targets and destroys human salivary gland cancer cells in laboratory and animal studies. This oncolytic HSV shows promise as a novel therapy for salivary carcinomas resistant to standard treatments.
Area of Science:
- Oncology
- Virology
- Cancer Therapy
Background:
- Oncolytic herpes simplex viruses (HSV) show potent antitumoral effects in preclinical and early clinical settings.
- Human salivary gland carcinomas are a group of malignancies with limited treatment options.
Purpose of the Study:
- To investigate the efficacy of an attenuated, replication-competent oncolytic HSV (NV1023) against human salivary gland carcinomas.
- To evaluate NV1023's ability to infect, replicate within, and induce cytotoxicity in salivary gland cancer cell lines and in vivo tumor models.
Main Methods:
- NV1023 infection and replication were assessed in mucoepidermoid carcinoma and adenocarcinoma cell lines using lacZ and viral plaque assays.
- Cytotoxicity was determined at various multiplicities of infection (MOI) by Day 7.
- Tumor volume reduction was measured in nude mice bearing flank tumors after intratumoral NV1023 injection.
Main Results:
- NV1023 successfully infected and replicated in all tested salivary gland carcinoma cell lines.
- High cytotoxicity (>95%) was observed in most cell lines at MOI 5, with mucoepidermoid carcinomas showing greater sensitivity at lower viral concentrations.
- Significant tumor volume reduction was achieved in vivo following a single intratumoral NV1023 injection.
Conclusions:
- Oncolytic herpes simplex virus NV1023 demonstrates significant efficacy in targeting, replicating within, and lysing human salivary gland carcinomas.
- NV1023 is a promising biologic agent for further investigation as a novel therapeutic strategy for patients with refractory salivary carcinomas.
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