ArticlePharmaceutical research2012
Distinct aggregation mechanisms of monoclonal antibody under thermal and freeze-thaw stresses revealed by hydrogen exchange.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Engineering Extended Release Profiles for Biologic Formulations via Chemical Cross-Linking of Poloxamer 407 Hydrogels.ACS omega · 2025Article
- Characterizing Monoclonal Antibody Aggregation Using Charge Detection Mass Spectrometry and Industry Standard Methods.Journal of the American Society for Mass Spectrometry · 2025Article
- Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Ion Mobility Mass Spectrometry (IM-MS) for Structural Biology: Insights Gained by Measuring Mass, Charge, and Collision Cross Section.Chemical reviews · 2023Review
- Stability Evaluation of the Biosimilar Monoclonal Antibody Using Analytical Techniques.Turkish journal of pharmaceutical sciences · 2023Article
- The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - Part 1: Higher molecular weight species and subvisible particle formation.International journal of pharmaceutics: X · 2022Article
- The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - part 2: Aggregate formation and oxidation.International journal of pharmaceutics: X · 2022Article
- Toward a proper interpretation of hydrogen exchange data in disordered proteins.Biophysical journal · 2021Article
- The effects of intramolecular and intermolecular electrostatic repulsions on the stability and aggregation of NISTmAb revealed by HDX-MS, DSC, and nanoDSF.Protein science : a publication of the Protein Society · 2021Article
- Comparison of the pH- and thermally-induced fluctuations of a therapeutic antibody Fab fragment by molecular dynamics simulation.Computational and structural biotechnology journal · 2021Article
- Cryoconcentration and 3D Temperature Profiles During Freezing of mAb Solutions in Large-Scale PET Bottles and a Novel Scale-Down Device.Pharmaceutical research · 2020Article
- Covalent Labeling/Mass Spectrometry of Monoclonal Antibodies with Diethylpyrocarbonate: Reaction Kinetics for Ensuring Protein Structural Integrity.Journal of the American Society for Mass Spectrometry · 2020Article
- ANTISOMA: A Computational Pipeline for the Reduction of the Aggregation Propensity of Monoclonal Antibodies.Advances in experimental medicine and biology · 2020Article
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- Impact of Tryptophan Oxidation in Complementarity-Determining Regions of Two Monoclonal Antibodies on Structure-Function Characterized by Hydrogen-Deuterium Exchange Mass Spectrometry and Surface Plasmon Resonance.Pharmaceutical research · 2018Article
- Next generation antibody drugs: pursuit of the 'high-hanging fruit'.Nature reviews. Drug discovery · 2018Review
- Molecular and functional analysis of monoclonal antibodies in support of biologics development.Protein & cell · 2018Review
- Rapid screening of IgG quality attributes - effects on Fc receptor binding.FEBS open bio · 2017Article
- 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
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAggregation of monoclonal antibodies (mAbs) is a common yet poorly understood issue in therapeutic development. There remains a need for high-resolution structural information about conformational changes and intermolecular contacts during antibody aggregation.
methodsWe used hydrogen exchange mass spectrometry (HX-MS) to compare the aggregation mechanism and resultant aggregate structures of the pharmaceutical antibody Bevacizumab under freeze-thaw (F/T) and thermal stresses.
resultsBevacizumab aggregation increased with number of F/T cycles and decreased with protein concentration. HX-MS showed native-like aggregates. Conversely, thermal stress triggered non-native aggregation at temperatures below melting point of the least stable CH2 domain. Under these conditions, HX was significantly enhanced in much of the Fab fragment while being decreased relative to native HX in CDRs. Analysis of intrinsic fluorescence Trp and extrinsic ANS dye binding supported structural differences between two antibody aggregates formed by F/T vs. thermal stresses.
conclusionsReduced hydrogen exchange in three CDRs suggests these residues may form strong intermolecular contacts in the antibody aggregates; regions of enhanced HX indicate unfolding. Residue level modeling methods with varying levels of atomistic detail were unable to identify aggregation patterns predictively.
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