Targeted Gene Transfer for Adenocarcinoma Using a Combination of Tumor-specific Antibody and Tissue-specific Promoter |
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| Authors: | Shuji Kurane John C Krauss Eiji Watari Reiji Kannagi Alfred E Chang Shoji Kudoh |
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| Institution: | Fourth Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602;Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602;Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, Ohio 441959;Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-0012;Division of Surgical Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109 |
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| Abstract: | 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. |
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| Keywords: | Anti-Lewis Y antigen antibody CEA promoter CVM enhancer Cationic liposome Tumor-specific gene expression |
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