Brinkmann Ulrich, Kontermann Roland E
a Roche Pharma Research and Early Development (pRED), Roche Innovation Center Munich , Im Nonnenwald, Penzberg , Germany.
b Institute of Cell Biology and Immunology, University of Stuttgart , Allmandring, Stuttgart , Germany.
MAbs. 2017 Feb/Mar;9(2):182-212. doi: 10.1080/19420862.2016.1268307.
During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The 'zoo' of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibodies, molecules with an IgG structure, and large complex molecules composed of different antigen-binding moieties often combined with dimerization modules. The application of sophisticated molecular design and genetic engineering has solved many of the technical problems associated with the formation of bispecific antibodies such as stability, solubility and other parameters that confer drug properties. These parameters may be summarized under the term 'developability'. In addition, different 'target product profiles', i.e., desired features of the bispecific antibody to be generated, mandates the need for access to a diverse panel of formats. These may vary in size, arrangement, valencies, flexibility and geometry of their binding modules, as well as in their distribution and pharmacokinetic properties. There is not 'one best format' for generating bispecific antibodies, and no single format is suitable for all, or even most of, the desired applications. Instead, the bispecific formats collectively serve as a valuable source of diversity that can be applied to the development of therapeutics for various indications. Here, a comprehensive overview of the different bispecific antibody formats is provided.
在过去二十年中，我们见证了用于治疗应用的双特异性抗体的显著发展。双特异性抗体的“动物园”中有许多不同种类，包括约100种不同形式，其中有仅由两种抗体的抗原结合位点组成的小分子、具有IgG结构的分子，以及由不同抗原结合部分（通常与二聚化模块结合）组成的大型复杂分子。复杂的分子设计和基因工程的应用解决了许多与双特异性抗体形成相关的技术问题，如稳定性、溶解性以及赋予药物特性的其他参数。这些参数可以用“可开发性”这一术语来概括。此外，不同的“目标产品概况”，即所产生的双特异性抗体的期望特征，要求能够获取多种形式。它们在结合模块的大小、排列、价态、灵活性和几何形状以及分布和药代动力学特性方面可能会有所不同。不存在生成双特异性抗体的“一种最佳形式”，也没有单一形式适用于所有甚至大多数期望的应用。相反，双特异性形式共同构成了宝贵的多样性来源，可应用于各种适应症治疗药物的开发。在此，提供了不同双特异性抗体形式的全面概述。
