当前位置: X-MOL 学术Comput. Struct. Biotechnol. J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Format and geometries matter: Structure-based design defines the functionality of bispecific antibodies.
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2020-05-14 , DOI: 10.1016/j.csbj.2020.05.006
Steffen Dickopf 1 , Guy J Georges 1 , Ulrich Brinkmann 1
Affiliation  

Multispecific antibodies can be generated in different formats. More than two decades of R&D in the field of bispecific antibody engineering revealed that the design and choice of format can have a profound impact on the antibody functionality. This holds in particular true for entities that elicit (inter-)cellular processes such as receptor activation, receptor internalization, receptor clustering or the formation of immunological synapses between two cells. This review covers design parameters that influence the functionality of multispecific formats, with particular focus on T cell-recruiting bispecific antibodies. We describe formats that display the same size and domain sequences but a varying geometry. The structural composition of (artificial) immune synapses is reviewed and allows conclusions why some formats that share size and domain composition are more effective than others. To support the statement that the geometry matters, we present the design of a recently designed antibody format that is characterized by its compact shape. The TriFab-Contorsbody consists of two tumor cell-targeting entities and one moiety for T cell recruitment. The unique barrel-like shape provides a 35-fold increase in potency compared to an IgG-like molecule with identical domain sequences.



中文翻译:

格式和几何形状很重要:基于结构的设计定义了双特异性抗体的功能。

多特异性抗体可以以不同的形式产生。在双特异性抗体工程领域超过二十年的研发表明,设计和格式选择可对抗体功能产生深远影响。对于引发(细胞间)过程,例如受体激活,受体内在化,受体簇化或两个细胞之间免疫突触形成的实体,尤其如此。这篇综述涵盖了影响多特异性形式功能的设计参数,尤其着眼于招募T细胞的双特异性抗体。我们描述了显示相同大小和域序列但几何形状不同的格式。审查(人工)免疫突触的结构组成,并得出结论,为什么共享大小和域组成的某些格式比其他格式更有效。为了支持几何学很重要的说法,我们提出了以其紧凑的形状为特征的最近设计的抗体形式的设计。TriFab-Contorsbody由两个靶向肿瘤细胞的实体和一个用于T细胞募集的部分组成。与具有相同结构域序列的IgG样分子相比,独特的桶形形状使效价提高了35倍。TriFab-Contorsbody由两个靶向肿瘤细胞的实体和一个用于T细胞募集的部分组成。与具有相同结构域序列的IgG样分子相比,独特的桶形形状使效价提高了35倍。TriFab-Contorsbody由两个靶向肿瘤细胞的实体和一个用于T细胞募集的部分组成。与具有相同结构域序列的IgG样分子相比,独特的桶形形状使效价提高了35倍。

更新日期:2020-05-14
down
wechat
bug