Sugiyama Y, Chen F A, Takita H, Bankert R B
Department of Molecular Immunology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Cancer Res. 1988 May 15;48(10):2768-73.
Monoclonal antibody 5E8 which is specific for a Mr 160,000 glycoprotein (gp160) on the surface of human lung cancer was radiolabeled with 125I. Radiolabeled 5E8 antibody is shown here to suppress the growth of gp160 positive human lung tumor cell lines in a dose-dependent fashion, but this same radiolabeled antibody does not alter the growth of gp160 negative lung tumor cell lines. Neither the unlabeled 5E8 nor a control radiolabeled monoclonal antibody has any effect upon the growth of gp160 positive tumors. The specificity of radiolabeled antibody mediated tumor killing is further demonstrated by the ability of unlabeled 5E8 to inhibit tumor killing by 125I-5E8. The efficiency with which the labeled tumor specific antibody suppressed tumor colony formation is enhanced by increasing the molar ratio of 125I to 5E8. This ratio could be increased to a level of two without affecting the capacity of the antibody to bind to the cell surface antigen. An attempt to increase the efficiency of tumor killing by the addition of a second antibody subsequent to incubation with 125I-5E8 was unsuccessful. These results indicate that 125I is a viable isotope and gp160 represents an appropriate target for radioimmunotherapy of human lung cancer.
对人肺癌表面一种分子量为160,000的糖蛋白(gp160)具有特异性的单克隆抗体5E8用125I进行了放射性标记。放射性标记的5E8抗体在此显示出以剂量依赖方式抑制gp160阳性人肺肿瘤细胞系的生长,但这种相同的放射性标记抗体不会改变gp160阴性肺肿瘤细胞系的生长。未标记的5E8和对照放射性标记单克隆抗体对gp160阳性肿瘤的生长均无任何影响。未标记的5E8抑制125I-5E8介导的肿瘤杀伤的能力进一步证明了放射性标记抗体介导的肿瘤杀伤的特异性。通过增加125I与5E8的摩尔比,标记的肿瘤特异性抗体抑制肿瘤集落形成的效率得以提高。该比例可提高到2,而不影响抗体与细胞表面抗原结合的能力。在与125I-5E8孵育后添加第二种抗体以提高肿瘤杀伤效率的尝试未成功。这些结果表明125I是一种可行的同位素,gp160是人类肺癌放射免疫治疗的合适靶点。