THE EFFICACY OF ADENOVIRUS-MEDIATED GENE-THERAPY OF OVARIAN-CANCER ISENHANCED BY USING THE CYTOMEGALOVIRUS PROMOTER

The cytomegalovirus(CMV) promoter is considered one of the strongest p ositive regulators. In this study toxicity, cell killing efficacy and bystander effect of Rous Sarcoma Virus(RSV) driven herpes simplex thym idine kinase(TK) gene therapy was compared with CMV driven TK gene the rapy in three ovarian cancer cell lines with different growth patterns using a 3-(4,5-dimethylthiazol)-2, 5-diphenyl tetra-zolium bromide (M TT) based assay. ADV/CMV-TK was shown to be 2 to 10 times more effecti ve in tumor cell killing than ADV/RSV-TK. The difference in cell killi ng efficacy between ADV/CMV-TK and ADV/RSV-TK was dependent on the ind ividual cell line. A CMV promoter dependent eight to ten fold improvem ent in cell killing efficacy was observed in the relatively slow growi ng SKOV3 cell line which is not easily transducible, while only a 2 to 4 fold difference was observed in the easily transducible OV-CA-2774 and OV-CA-1225 cell lines. ADV/CMV-TK also showed a stronger bystander effect than ADV/RSV-TK in all three ovarian cancer cell lines. Our da ta demonstrated that the efficacy of adenovirus-mediated gene therapy of ovarian cancer can be enhanced by using the CMV promoter without in creasing toxicity.