For the targeting delivery of therapeutic genes specifically to prostate cancer, we have developed a transfection system using anti-prostate-specific membrane antigen (PSMA) monoclonal antibody (mAb). PSMA is a transmembrane protein predominantly expressed on human neoplastic prostate epithelial cells and up-regulated following hormone ablation therapy. In our gene delivery system, PSMA mAbs were conjugated with a cationic polymer, polyethyleneimine (PEI) to form an affinity complex with plasmid DNA. PSMA mAbs and PEI were biotinylated and bound via avidin. This mAb/PEI/DNA complex was designated as Immunogene. With this novel gene delivery system, a luciferase reporter gene was preferentially introduced into PSMA-expressing prostate cancer cells, LNCaP and C4-2, but not into PSMA-negative DU145 and PC-3 prostate cancer cells. Thus, we propose the Immunogene approach with PSMA mAbs is capable of providing an antigen-specific gene delivery system for various targeting gene therapy strategies in prostate cancer and can be potentially used even with the clinically conventional androgen ablation therapies.
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