Targeted Gene Transfer for Adenocarcinoma Using a Combination of Tumor‐specific Antibody and Tissue‐specific Promoter

We have developed a highly specific gene transfer method for adenocarcinoma using a monoclonal antibody against tumor‐specific antigen coupled with a plasmid containing the carcinoembryonic antigen (CEA)‐specific promoter. The chimeric CEA promoter (CC promoter), which contained an enhancer from the immediate early gene of cytomegalovirus and the CEA promoter, achieved 4‐ to 5‐fold higher transgene expression in CEA‐producing cells than the original CEA promoter while maintaining CEA specificity. Furthermore, a complex of a monoclonal antibody against Lewis Y antigen (LYA), the CC promoter‐containing plasmid and cationic liposomes (DOTAP) achieved specific gene expression in CEA‐producing and LYA‐positive adenocarcinoma cell lines that was 200‐fold more efficient than in CEA‐non‐producing and LYA‐negative cell lines during a short in vitro incubation. This strategy may be applicable for clinical gene therapy.