Characterization of mAb dimers reveals predominant dimer forms common in therapeutic mAbs

Plath, Friederike and Ringler, Philippe and Graff-Meyer, Alexandra and Stahlberg, Henning and Lauer, Matthias E. and Rufer, Arne C. and Graewert, Melissa A. and Svergun, Dmitri and Gellermann, Gerald and Finkler, Christof and Stracke, Jan O. and Koulov, Atanas and Schnaible, Volker. (2016) Characterization of mAb dimers reveals predominant dimer forms common in therapeutic mAbs. mAbs, 8 (5). pp. 928-940.

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Official URL: http://edoc.unibas.ch/42335/

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The formation of undesired high molecular weight species such as dimers is an important quality attribute for therapeutic monoclonal antibody formulations. Therefore, the thorough understanding of mAb dimerization and the detailed characterization mAb dimers is of great interest for future pharmaceutical development of therapeutic antibodies. In this work, we focused on the analyses of different mAb dimers regarding size, surface properties, chemical identity, overall structure and localization of possible dimerization sites. Dimer fractions of different mAbs were isolated to a satisfactory purity from bulk material and revealed two predominant overall structures, namely elongated and compact dimer forms. The elongated dimers displayed one dimerization site involving the tip of the Fab domain. Depending on the stress applied, these elongated dimers are connected either covalently or non-covalently. In contrast, the compact dimers exhibited non-covalent association. Several interaction points were detected for the compact dimers involving the hinge region or the base of the Fab domain. These results indicate that mAb dimer fractions are rather complex and may contain more than one kind of dimer. Nevertheless, the overall appearance of mAb dimers suggests the existence of two predominant dimeric structures, elongated and compact, which are commonly present in preparations of therapeutic mAbs.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Stahlberg)
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology and Biophysics (Engel)
UniBasel Contributors:Stahlberg, Henning and Ringler, Philippe
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Taylor & Francis
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2023 11:43
Deposited On:22 Nov 2016 08:23

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