Li S, Zhang X Y, Zhang S Y, Chen X T, Chen L J, Shu Y H, Zhang J L, Fan D M
Laboratory of Gastroenterology, Xijing Hospital, Xi'an, Shaanxi Province, China.
Bioconjug Chem. 1990 Jul-Aug;1(4):245-50. doi: 10.1021/bc00004a003.
In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced.
在本研究中，选择一种抗胃癌单克隆抗体MGb2，以葡聚糖T-40作为中间体来制备抗体-丝裂霉素C偶联物。每分子抗体可特异性结合多达20分子的丝裂霉素C，且不会显著损害抗体的抗原结合能力和丝裂霉素C的药理活性。该偶联物在体外对人胃癌细胞系SGC-7901表现出选择性细胞毒性。放射免疫显像和生物分布研究表明，通过葡聚糖T-40作为中间体与丝裂霉素C偶联后，抗体的肿瘤定位能力得以很好地保留。在双侧肾包膜下接种人胃癌GAII的裸鼠中进行测试时，以1mg/kg药物的剂量每周两次腹腔注射该偶联物，持续3周，肿瘤抑制率为152.29%，结果远优于游离丝裂霉素C或无关偶联物。在另一种人胃癌SGC-7901裸鼠模型中也发现了类似结果。同时，与抗体偶联后，丝裂霉素C对受试动物的毒性显著降低。
