Ikegami Shusei, Yamakami Kazuo, Ono Takeshi, Sato Masaki, Suzuki Satoshi, Yoshimura Ichiro, Asano Tomohiko, Hayakawa Masamichi, Tadakuma Takushi
Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359, Japan.
Hum Gene Ther. 2006 Oct;17(10):997-1005. doi: 10.1089/hum.2006.17.997.
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.
前列腺特异性膜抗原（PSMA）是一种在前列腺癌细胞表面表达的膜结合抗原，本文描述了使用抗PSMA抗体进行靶向基因治疗。我们将抗PSMA单克隆抗体与聚-L-赖氨酸偶联，然后与质粒一起孵育。然后用阳离子脂质体将这些复合物转染到细胞中。在PSMA阳性的LNCaP细胞中，抗PSMA-脂质体复合物的转染效率高于正常IgG-脂质体复合物。此外，含有自杀基因胸苷激酶的抗PSMA-脂质体复合物在体外对LNCaP细胞表现出选择性生长抑制作用，但对PSMA阴性细胞没有显著影响。在裸鼠LNCaP细胞的体内异种移植模型中，我们通过尾静脉注射复合物。根据5-溴-4-氯-3-吲哚基-β-D-吡喃半乳糖苷（X-Gal）染色和荧光素酶测定结果判断，与正常IgG-脂质体复合物相比，抗PSMA-脂质体复合物在LNCaP异种移植瘤中观察到质粒DNA的显著富集。然而，质粒DNA在包括肝脏、肾脏、肺和脾脏在内的任何其他器官中的分布没有实质性变化。此外，在自杀基因治疗中，与正常IgG-脂质体复合物相比，抗PSMA-脂质体复合物对LNCaP异种移植瘤的生长具有显著抑制作用。
