Genmab, Utrecht, Netherlands.
The Antibody Society, Framingham, MA, USA.
Nat Rev Drug Discov. 2019 Aug;18(8):585-608. doi: 10.1038/s41573-019-0028-1.
The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities - that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.
双特异性抗体（bsAb）这一术语用于描述一大类旨在识别两种不同表位或抗原的分子。bsAb 有多种形式，从相对较小的蛋白质，仅由两个连接的抗原结合片段组成，到具有附加结构域的大型免疫球蛋白 G（IgG）样分子。bsAb 的一个吸引人的特征是它们具有潜在的新功能——也就是说，不存在于亲本或参考抗体混合物中的活性。在这些所谓的必需 bsAb 中，两个结合特异性的物理连接产生了一种依赖性，可以是时间依赖性的，即结合事件依次发生，也可以是空间依赖性的，即结合事件同时发生，例如将效应器与靶细胞连接。迄今为止，已经有超过 20 种不同的商业化 bsAb 创造和开发技术平台，有 2 种 bsAb 已上市，超过 85 种处于临床开发阶段。在这里，我们从机制的角度综述 bsAb 的现状，包括对该领域的全面概述。
