Effective treatment of head and neck squamous cell carcinoma by an oncolytic herpes simplex virus
Richard J Wong ; Se-Heon Kim ; Yuman Fong ; Paul A Johnson ; Jatin P Shah ; John K Joe
Journal of the American College of Surgeons, Vol.193(1) : 12~21, 2001
Journal of the American College of Surgeons
The prognosis of patients with advanced or recurrent head and neck squamous cell carcinoma remains poor despite refinements in multimodality therapies. This study evaluates the efficacy of a replication-competent, attenuated, oncolytic herpes simplex virus, NV1020, as a novel agent in the treatment of human head and neck squamous cell carcinoma (HNSCC).
Five different HNSCC lines were exposed to NV1020 in vitro at varying viral concentrations. The ability of the virus to lyse and replicate within these cancer cells in vitro was determined by cytotoxicity assay and plaque assay, respectively. Three HNSCC lines were grown in the subcutaneous flanks of athymic nude mice and treated with an intratumoral injection of NV1020 or saline as a control. Tumor dimensions were subsequently measured at serial time points and tumor volumes were calculated. Herpes simplex virus (HSV)-1 immunohistochemistry was performed on excised tumors to determine the efficacy of in vivo tumor infection by NV1020.
NV1020 was highly cytotoxic in vitro to all five human HNSCC lines at a concentration of one infectious viral particle per cancer cell, and had variable cytotoxicity at a 100-fold lower concentration. Viral replication in vitro by NV1020 was efficient in four of five HNSCC lines with a greater than 200-fold increase in viral titers. Flank tumors treated with intratumoral injections of NV1020 resulted in significant regression of all tested HNSCC lines. HSV-1 immunohistochemistry of excised flank tumors treated with NV1020 demonstrated positive cytoplasmic staining and areas of tumor necrosis at 24 hours after injection.
NV1020 is an oncolytic HSV that displays efficient replication and oncolysis in human HNSCC lines in vitro. Injection of NV1020 into murine flank tumors demonstrated effective tumor regression. Treatment of HNSCC with NV1020 is a promising form of therapy with potential clinical applicability in humans.