ADENOVIRUS-MEDIATED THYMIDINE KINASE GENE TRANSDUCTION IN HUMAN EPITHELIAL OVARIAN-CANCER CELL-LINES FOLLOWED BY EXPOSURE TO GANCICLOVIR

In an effort to develop gene therapy for ovarian cancer efficacy and t oxicity of adenovirus-mediated transfer of the HSV-TK gene followed by administration of ganciclovir were studied in two human epithelial ov arian cancer cell lines Ov-ca-2774 and Ov-ca-1225. 100% transduction w as achieved in both cell lines at MOIs of 7 and 15 as demonstrated by X-Gal staining. No toxicity of virus alone was observed at MOIs up to 30. GCV was not toxic up to 200 mu g/ml. Cell killing efficacy was sho wn to be dependent on MOI as well as GCV dose. The ''bystander effect' ' of ADV/RSV-TK was quantified by mixing experiments and found to be d ependent on the proportion of ADV/RSV-TK positive cells as well as the GCV dosage. Similar results were observed in both cell lines. ADV/RSV -TK mediated gene therapy may be a promising approach in ovarian cance r.