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


METHODS
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.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Daniel L
DL
Price
Shu-Fu
SF
Lin
Ziqun
Z
Han
Guy
G
Simpson
Robert S
RS
Coffin
Joyce
J
Wong
Sen
S
Li
Yuman
Y
Fong
Richard J
RJ
Wong
D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000096:biosynthesis; D005437:Flucytosine / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics; D050130:Oncolytic Virotherapy; D011355:Prodrugs / Q000627:therapeutic use*
D011355:Prodrugs; D005437:Flucytosine; D043525:Cytosine Deaminase