Targeting Gene Therapy for Prostate Cancer Cells by Liposomes Complexed with Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody

Abstract

Prostate-specific membrane antigen (PSMA) is a membrane-bound antigen expressed on the surface of prostate cancer cells, and this paper describes the use of an antibody against PSMA for targeting gene therapy. We coupled anti-PSMA monoclonal antibody with poly-L-lysine and then incubated it with plasmids. These complexes were then transfected with cationic liposomes into cells. The transfection efficiency of anti-PSMA– liposome complex was higher than that of normal IgG–liposome complex in PSMA-positive LNCaP cells. Furthermore, anti-PSMA–liposome complex containing a suicide gene, thymidine kinase, demonstrated a selective growth-inhibitory effect on LNCaP cells in vitro, but did not exert a significant effect on PSMA-negative cells. In an in vivo xenograft model of LNCaP cells in nu/nu mice, we administered the complexes via the tail vein. Judging on the basis of both 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside (X-Gal) staining and luciferase assay findings, a significant enrichment of plasmid DNA was observed in LNCaP xenografts with anti-PSMA–liposome complex in comparison with normal IgG–liposome complex. However, the distribution of plasmid DNA did not change substantially in any other organs including the liver, kidney, lung, and spleen. Moreover, in suicide gene therapy, anti-PSMA–liposome complex exerted a significant inhibitory effect on the growth of LNCaP xenograft, in contrast to normal IgG–liposome complex.