ADENOVIRUS-MEDIATED GENE-THERAPY OF GASTRIC-CARCINOMA USING CANCER-SPECIFIC GENE-EXPRESSION IN-VIVO

The carcinoembryonic antigen (CEA) is a glycoprotein which overexpress ed in the majority of human gastric cancers, We demonstrated that reco mbinant adenoviral vector (AdCEAtk), containing the CEA promoter, coul d transfer the herpes simplex virus thymidine kinase (HSVtk) gene into CEA-producing gastric cancer cells to confer sensitivity to ganciclov ir (GCV) in vivo. In an ex vivo experiment, the tumor growth was inhib ited after GCV treatment when the tumor contained more than 20% of AdC EAtk infected cells, indicating an efficient bystander killing effect, With intra-tumoral injection of AdCEAtk, the HSVtk were selectively e xpressed in approximately 30% of CEA producing cancer cells, By AdCEAt k injection and GCV administration, the growth of tumors was significa ntly inhibited by 20% as compared to untreated tumors. It is hoped tha t these results provide a strategy of tumor specific gene transfer for CEA producing gastric cancers. (C) 1997 Academic Press.