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Antibodies 2016, 5(3), 19; doi:10.3390/antib5030019

Antibody Aggregation: Insights from Sequence and Structure

1
Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
2
Intrexon Corporation, Germantown, MD 20876, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Mark Cragg
Received: 12 May 2016 / Revised: 3 August 2016 / Accepted: 4 August 2016 / Published: 5 September 2016
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Abstract

Monoclonal antibodies (mAbs) are the fastest-growing biological therapeutics with important applications ranging from cancers, autoimmunity diseases and metabolic disorders to emerging infectious diseases. Aggregation of mAbs continues to be a major problem in their developability. Antibody aggregation could be triggered by partial unfolding of its domains, leading to monomer-monomer association followed by nucleation and growth. Although the aggregation propensities of antibodies and antibody-based proteins can be affected by the external experimental conditions, they are strongly dependent on the intrinsic antibody properties as determined by their sequences and structures. In this review, we describe how the unfolding and aggregation susceptibilities of IgG could be related to their cognate sequences and structures. The impact of antibody domain structures on thermostability and aggregation propensities, and effective strategies to reduce aggregation are discussed. Finally, the aggregation of antibody-drug conjugates (ADCs) as related to their sequence/structure, linker payload, conjugation chemistry and drug-antibody ratio (DAR) is reviewed. View Full-Text
Keywords: monoclonal antibodies; antibody aggregation; protein unfolding; antibody domains; antibody drug conjugates monoclonal antibodies; antibody aggregation; protein unfolding; antibody domains; antibody drug conjugates
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Li, W.; Prabakaran, P.; Chen, W.; Zhu, Z.; Feng, Y.; Dimitrov, D.S. Antibody Aggregation: Insights from Sequence and Structure. Antibodies 2016, 5, 19.

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