Selective gene therapy for prostate cancer cells using liposomes conjugated with IgM type monoclonal antibody against prostate-specific membrane antigen.
Prostate cancer cells express prostate-specific membrane antigen (PSMA). We developed an IgM type monoclonal antibody against PSMA. The antibody was coupled to poly-L-lysine and thereafter this conjugate was mixed with cationic liposomes containing plasmid DNA. The antibody-liposome complex was tested whether it could deliver the gene of interest selectively to the PSMA positive cells. As assessed by beta-galactosidase reporter gene, the transfection efficiency was 13.2% with anti-PSMA-liposome complex as compared to 4% with control IgM liposome complex. In contrast, no such differences were observed in PSMA negative PC-3, DU145 and T24 cells. Furthermore, in the suicide gene therapy in vitro with thymidine kinase gene plus ganciclovir system, anti-PSMA liposome complex demonstrated a selective growth inhibitory effect on PSMA positive LNCaP cells but not on PSMA negative cell lines.
Ikegami
Shusei
S
Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Tadakuma
Takushi
T
Yamakami
Kazuo
K
Ono
Takeshi
T
Suzuki
Satoshi
S
Yoshimura
Ichiro
I
Asano
Tomohiko
T
Hayakawa
Masamichi
M
D000230:Adenocarcinoma / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism; D004247:DNA; D018390:Gene Targeting; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage* / Q000378:metabolism; D008081:Liposomes; D008297:Male; D010957:Plasmids / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D008081:Liposomes; D004247:DNA; D017430:Prostate-Specific Antigen