Oncolysis using herpes simplex virus type 1 engineered to express cytosine deaminase and a fusogenic glycoprotein for head and neck squamous cell carcinoma.

Overview

OBJECTIVE: To determine if prodrug conversion of fluorocytosine to fluorouracil by an engineered herpes virus, OncoVEX(GALV/CD), enhances oncolytic therapy of head and neck squamous cell carcinoma. DESIGN: We assessed the ability of OncoVEX(GALV/CD) and OncoVEX(GFP) to infect, replicate within, and lyse 4 head and neck squamous cell carcinoma lines in vitro. The effects of adding fluorocytosine with OncoVEX(GALV/CD) were evaluated. RESULTS: Head and neck squamous cell carcinoma was permissive to green fluorescent protein expression in100% of cells by OncoVEX(GFP) at a multiplicity of infection of 1 after 48 hours and supported logarithmic viral replication. Virus caused more than 60% cell death 6 days after exposure to virus at a multiplicity of infection of 0.1 in 3 of the 4 cell lines. Fluorocytosine did not enhance cytotoxicity induced by OncoVEX(GALV/CD) at a multiplicity of infection of 0.1. However, for the least-sensitive SCC25 cell line, virus at a multiplicity of infection of 0.01 was cytotoxic to only 4% of cells after 6 days but was cytotoxic to 35% of cells with fluorocytosine. CONCLUSIONS: OncoVEX(GALV/CD) efficiently infects, replicates within, and lyses head and neck squamous cell carcinoma at relatively low viral doses. Prodrug conversion by cytosine deaminase did not enhance therapy at viral doses that cause efficient cytotoxicity but may have beneficial effects in less-sensitive cell lines at low viral doses.