Burstein S, Knapp R
J Med Chem. 1977 Jul;20(7):950-2. doi: 10.1021/jm00217a018.
Antibodies with specificity for an experimental ovarian carcinoma were coupled to methotrexate by two procedures. Water-soluble carbodiimide gave effective coupling, but a large proportion of the conjugate was rendered insoluble, presumably due to alteration or aggregation of the antibodies. A modification of the mixed anhydride procedure gave rise to products which were completely soluble and allowed a high degree of coupling to be achieved. In vivo testing of the conjugates revealed a significant increase in survival time in treated mice when compared to a variety of control groups; these included groups receiving antiserum or drug alone, mixtures of the two, and conjugates of normal gamma-globulin with methotrexate. Our results provide added support for the concept that tumor-associated antibodies coupled to cytotoxic agents are more effective than single agents or noncoupled mixtures of agents.
通过两种方法将对实验性卵巢癌具有特异性的抗体与甲氨蝶呤偶联。水溶性碳二亚胺实现了有效的偶联，但大部分偶联物变得不溶，推测是由于抗体的改变或聚集。混合酸酐法的一种改进产生了完全可溶的产物，并实现了高度的偶联。与各种对照组相比，对这些偶联物进行的体内测试显示，治疗小鼠的存活时间显著增加；这些对照组包括单独接受抗血清或药物的组、两者的混合物以及正常γ球蛋白与甲氨蝶呤的偶联物。我们的结果为以下概念提供了更多支持，即与细胞毒性剂偶联的肿瘤相关抗体比单一药物或未偶联的药物混合物更有效。
