Targeting gene therapy for prostate cancer cells by liposomes complexed with anti-prostate-specific membrane antigen monoclonal antibody.
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-beta-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.
Ikegami
Shusei
S
Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359, Japan.
Yamakami
Kazuo
K
Ono
Takeshi
T
Sato
Masaki
M
Suzuki
Satoshi
S
Yoshimura
Ichiro
I
Asano
Tomohiko
T
Hayakawa
Masamichi
M
Tadakuma
Takushi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D008081:Liposomes; D017430:Prostate-Specific Antigen