Goldmacher Victor S, Kovtun Yelena V
ImmunoGen, Inc., 830 Winter Street, Waltham, MA 02451-1477, USA.
Ther Deliv. 2011 Mar;2(3):397-416. doi: 10.4155/tde.10.98.
One approach to improving activity of anticancer drugs is to conjugate them to antibodies that recognize tumor-associated, cell-surface antigens. The antibody-drug conjugate concept evolved following major advances, first, in the development of humanized and fully human antibodies; second, in the discoveries of highly cytotoxic compounds ('drugs) linkable to antibodies; and finally, in the optimization of linkers that couple the drug to the antibody and provide sufficient stability of the antibody-drug conjugate in the circulation, optimal activation of the drug in the tumor, and the ability of the activated drug to overcome multidrug resistance. In this article, we will review the considerations for selecting a target antigen, the design of the conjugate, and the pre-clinical and clinical experiences with the current generation of antibody-drug conjugates.
提高抗癌药物活性的一种方法是将它们与识别肿瘤相关细胞表面抗原的抗体偶联。抗体 - 药物偶联物的概念是在以下主要进展之后演变而来的：首先，在人源化和全人源抗体的开发方面；其次，在可与抗体连接的高细胞毒性化合物（“药物”）的发现方面；最后，在优化连接子方面，该连接子将药物与抗体偶联，并在循环中提供抗体 - 药物偶联物足够的稳定性、在肿瘤中药物的最佳激活以及激活药物克服多药耐药性的能力。在本文中，我们将综述选择靶抗原的考量因素、偶联物的设计以及当前一代抗体 - 药物偶联物的临床前和临床经验。
