ArticleProtein science : a publication of the Protein Society2010
The use of native cation-exchange chromatography to study aggregation and phase separation of monoclonal antibodies.
Article in Protein science : a publication of the Protein Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 58 citations in OpenAlex.
- Separation of Monoclonal Antibody Aggregates Using an Analytical Ultrafiltration Technique.Membranes · 2026Article
- Fate of Stressed Oligoclonal Antibodies Tracked by Fluorescence Cross-Correlation Spectroscopy: IgG Aggregation Proceeds across the Species Barrier.Analytical chemistry · 2025Article
- Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation.Frontiers in bioengineering and biotechnology · 2023Article
- Coformulation of Broadly Neutralizing Antibodies 3BNC117 and PGT121: Analytical Challenges During Preformulation Characterization and Storage Stability Studies.Journal of pharmaceutical sciences · 2018Article
- Probing Conformational Diversity of Fc Domains in Aggregation-Prone Monoclonal Antibodies.Pharmaceutical research · 2018Article
- Characterization of Aggregation Propensity of a Human Fc-Fusion Protein Therapeutic by Hydrogen/Deuterium Exchange Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2017Article
- Remediating agitation-induced antibody aggregation by eradicating exposed hydrophobic motifs.mAbs · 2014Article
- Article
- Phase transitions in human IgG solutions.The Journal of chemical physics · 2013Article
- Aggregation mechanism of an IgG2 and two IgG1 monoclonal antibodies at low pH: from oligomers to larger aggregates.Pharmaceutical research · 2013Article
- Pathological crystallization of human immunoglobulins.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Elucidation of acid-induced unfolding and aggregation of human immunoglobulin IgG1 and IgG2 Fc.The Journal of biological chemistry · 2012Article
- Distinct aggregation mechanisms of monoclonal antibody under thermal and freeze-thaw stresses revealed by hydrogen exchange.Pharmaceutical research · 2012Article
- Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Classification and characterization of therapeutic antibody aggregates.The Journal of biological chemistry · 2011Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
This study introduces a novel analytical approach for studying aggregation and phase separation of monoclonal antibodies (mAbs). The approach is based on using analytical scale cation-exchange chromatography (CEX) for measuring the loss of soluble monomer in the case of individual and mixed protein solutions. Native CEX outperforms traditional size-exclusion chromatography in separating complex protein mixtures, offering an easy way to assess mAb aggregation propensity. Different IgG1 and IgG2 molecules were tested individually and in mixtures consisting of up to four protein molecules. Antibody aggregation was induced by four different stress factors: high temperature, low pH, addition of fatty acids, and rigorous agitation. The extent of aggregation was determined from the amount of monomeric protein remaining in solution after stress. Consequently, it was possible to address the role of specific mAb regions in antibody aggregation by co-incubating Fab and Fc fragments with their respective full-length molecules. Our results revealed that the relative contribution of Fab and Fc regions in mAb aggregation is strongly dependent on pH and the stress factor applied. In addition, the CEX-based approach was used to study reversible protein precipitation due to phase separation, which demonstrated its use for a broader range of protein-protein association phenomena. In all cases, the role of Fab and Fc was clearly dissected, providing important information for engineering more stable mAb-based therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.