Kojima S, Suzuki N, Kubota K, Shimura N, Kubodera A, Yamaguchi T, Takahashi T, Oyamada H
Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.
Nucl Med Biol. 1993 Feb;20(2):197-202. doi: 10.1016/0969-8051(93)90115-b.
The specificity of A7 monoclonal antibody (A7 MoAb), raised against a human colon cancer, was investigated in detail and compared with that of anti-CEA MoAb. Firstly, the biodistributions of radiolabeled A7 MoAb and anti-CEA MoAb were examined in human colon cancer (LS-174T)-, glioblastoma- and lung cancer (Lu-65)-bearing nude mice. 125I-A7 MoAb was highly concentrated into LS-174T and also, to a lesser extent, in glioblastoma, whereas 125I-anti-CEA MoAb was significantly taken up only by LS-174T. Both of these antibodies were taken up at only very low concentrations into Lu-65. Secondly, in vitro binding studies of 125I-A7 MoAb and 125I-anti-CEA MoAb with LS-174T cells and glioblastoma cells revealed high binding activity of these MoAbs to LS-174T cells, though A7 MoAb had a much higher affinity than that of anti-CEA MoAb. Neither of them showed high affinity for glioblastoma cells. Thirdly, competitive binding assay using A7 MoAb and anti-CEA MoAb to LS-174T cells showed that the binding of each 125I-MoAb was not inhibited by the other MoAb. Finally, in radioimmuno-imaging studies of LS-174T- and glioblastoma-bearing mice with 131I-A7 MoAb and -anti-CEA MoAb, both tumors were clearly visualized with the former, while the latter visualized only LS-174T. The A7 MoAb is clearly different from anti-CEA MoAb and may be useful for the in vivo radioimmunodetection and treatment of colon cancer.
详细研究了针对人结肠癌产生的A7单克隆抗体(A7 MoAb)的特异性,并与抗CEA单克隆抗体进行了比较。首先,在荷人结肠癌(LS-174T)、胶质母细胞瘤和肺癌(Lu-65)的裸鼠中检测了放射性标记的A7单克隆抗体和抗CEA单克隆抗体的生物分布。125I-A7单克隆抗体高度浓集于LS-174T,在胶质母细胞瘤中浓集程度较低,而125I-抗CEA单克隆抗体仅被LS-174T显著摄取。这两种抗体在Lu-65中的摄取浓度都非常低。其次,125I-A7单克隆抗体和125I-抗CEA单克隆抗体与LS-174T细胞和胶质母细胞瘤细胞的体外结合研究表明,这些单克隆抗体对LS-174T细胞具有高结合活性,尽管A7单克隆抗体的亲和力远高于抗CEA单克隆抗体。它们对胶质母细胞瘤细胞均未显示出高亲和力。第三,使用A7单克隆抗体和抗CEA单克隆抗体对LS-174T细胞进行竞争结合试验表明,每种125I-单克隆抗体的结合均未被另一种单克隆抗体抑制。最后,在荷LS-174T和胶质母细胞瘤的小鼠中用131I-A7单克隆抗体和-抗CEA单克隆抗体进行放射免疫显像研究,前者能清晰显示两种肿瘤,而后者仅能显示LS-174T。A7单克隆抗体与抗CEA单克隆抗体明显不同,可能对结肠癌的体内放射免疫检测和治疗有用。