Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
Roche Pharma Research and Early Development (pRED), Large Molecule Research, Roche Innovation Center Penzberg, Penzberg, Germany.
Drug Discov Today. 2015 Jul;20(7):838-47. doi: 10.1016/j.drudis.2015.02.008. Epub 2015 Feb 26.
Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also place targets into close proximity, either to support protein complex formation on one cell, or to trigger contacts between cells. Examples of 'forced-connection' functionalities are bsAbs that support protein complexation in the clotting cascade, or tumor-targeted immune cell recruiters and/or activators. Following years of research and development (R&D), the first bsAb was approved in 2009. Another bsAb entered the market in December 2014 and several more are in clinical trials. Here, we describe the potentials of bsAbs to become the next wave of antibody-based therapies, focusing on molecules in clinical development.
双特异性抗体 (bsAbs) 结合了两种抗体的特异性,同时针对不同的抗原或表位。具有“双靶”功能的 bsAbs 可以干扰多个相关的表面受体或配体,例如与癌症、增殖或炎症过程相关的受体或配体。bsAbs 还可以将靶标置于接近的位置,要么支持一个细胞上的蛋白质复合物形成,要么触发细胞之间的接触。“强制连接”功能的例子是 bsAbs,它支持凝血级联中的蛋白质复合物形成,或者肿瘤靶向免疫细胞招募剂和/或激活剂。经过多年的研究和开发 (R&D),第一种 bsAb 于 2009 年获得批准。另一种 bsAb 于 2014 年 12 月进入市场,还有更多的 bsAb 处于临床试验阶段。在这里,我们描述了 bsAbs 成为下一代基于抗体的治疗方法的潜力,重点介绍处于临床开发阶段的分子。