Large Molecule Research, Pharma Research and Early Development, Roche Dignostics GmbH, Penzberg, Germany.
PLoS One. 2013 Apr 17;8(4):e61953. doi: 10.1371/journal.pone.0061953. Print 2013.
Bispecific antibodies are considered as a promising class of future biotherapeutic molecules. They comprise binding specificities for two different antigens, which may provide additive or synergistic modes of action. There is a wide variety of design alternatives for such bispecific antibodies, including the "CrossMab" format. CrossMabs contain a domain crossover in one of the antigen-binding (Fab) parts, together with the "knobs-and-holes" approach, to enforce the correct assembly of four different polypeptide chains into an IgG-like bispecific antibody. We determined the crystal structure of a hAng-2-binding Fab in its crossed and uncrossed form and show that CH1-CL-domain crossover does not induce significant perturbations of the structure and has no detectable influence on target binding.
双特异性抗体被认为是一类有前途的未来生物治疗分子。它们包含针对两种不同抗原的结合特异性，这可能提供附加或协同作用模式。有各种各样的设计选择用于这种双特异性抗体，包括“CrossMab”格式。CrossMabs 在一个抗原结合（Fab）部分中包含一个结构域交叉，以及“knobs-and-holes”方法，以强制将四个不同的多肽链组装成 IgG 样双特异性抗体。我们确定了 hAng-2 结合 Fab 的交联和未交联形式的晶体结构，并表明 CH1-CL 结构域交叉不会引起结构的显著扰动，并且对靶标结合没有可检测的影响。
