IMPROVEMENT OF GENE-THERAPY FOR OVARIAN-CANCER BY USING ACYCLOVIR INSTEAD OF GANCICLOVIR IN ADENOVIRUS-MEDIATED THYMIDINE KINASE GENE-THERAPY

Adenovirus(ADV) mediated thymidine kinase(TK) gene therapy followed by ganciclovir (GCV) administration is widely used in different types of cancer. ACV shares the same mechanism of selective cell killing in AD V/TK positive cells as GCV and can be wed at 4.5 times higher doses in patients without significant side effects. An increased dose of TK su bstrate Is associated with improved bystander effect and more efficien t cell killing. Toxicity and cell killing efficacy were assessed using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide(MTT) based assay in three ovarian cancer cell lines with different proliferation patterns. At the same concentration, equal ol higher cell killing eff icacy and bystander effect were observed using ACV rather than GCV. 2. 5 and 5 times (25 mu g/ml and 50 mu g/ml) higher concentrations of ACV always resulted in more effective cell killing than GCV (10 mu g/ml, P<O.01). Our data indicate that replacing GCV with ACV in the ADV- TK gene therapy may increase the treatment effect without increasing toxi city.