ArticlePharmaceutical research2013
Aggregation mechanism of an IgG2 and two IgG1 monoclonal antibodies at low pH: from oligomers to larger aggregates.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Protective Effect of Curcumin on Thermally Aggregated Bovine Serum Albumin.Cell biochemistry and biophysics · 2025Article
- Interdomain Interactions Modulate Refolding Kinetics and Aggregation in a Monoclonal Antibody.Journal of the American Society for Mass Spectrometry · 2025Article
- Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems.Pharmaceutical research · 2025Article
- Antibody Aggregate Removal by Multimodal Chromatography.Molecules (Basel, Switzerland) · 2025Review
- Article
- Real-Time Assessment of the Size Changes of Individual Sub-Visible Protein Particles under Buffer Variations: A Microfluidic Study.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Assessment of Functional Characterization and Comparability of Biotherapeutics: a Review.The AAPS journal · 2021Review
- Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods.International journal of molecular sciences · 2021Article
- Article
- Investigating the Impact of Sample Preparation on Mass Spectrometry-Based Drug-To-Antibody Ratio Determination for Cysteine- and Lysine-Linked Antibody-Drug Conjugates.Antibodies (Basel, Switzerland) · 2020Article
- Surfaces Affect Screening Reliability in Formulation Development of Biologics.Pharmaceutical research · 2020Article
- Modelling of pH-dependence to develop a strategy for stabilising mAbs at acidic steps in production.Computational and structural biotechnology journal · 2020Review
- Article
- Characterizing Thermal Transitions of IgG with Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2019Article
- Solution pH jump during antibody and Fc-fusion protein thaw leads to increased aggregation.Journal of pharmaceutical analysis · 2018Article
- Parallel chromatography and in situ scattering to interrogate competing protein aggregation pathways.Protein science : a publication of the Protein Society · 2018Article
- Formation of multimeric antibodies for self-delivery of active monomers.Drug delivery · 2017Article
- AlphaScreen-based homogeneous assay using a pair of 25-residue artificial proteins for high-throughput analysis of non-native IgG.Scientific reports · 2017Article
- Selective inhibition of aggregation/fibrillation of bovine serum albumin by osmolytes: Mechanistic and energetics insights.PloS one · 2017Article
- Identifying protein aggregation mechanisms and quantifying aggregation rates from combined monomer depletion and continuous scattering.Analytical biochemistry · 2016Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo identify the aggregation mechanism and the stability characteristics of three different monoclonal antibodies under acidic conditions.
methodsThe aggregation kinetics is analyzed by a combination of light scattering, size exclusion chromatography and fluorescence techniques and the aggregation data are correlated to protein structure, hydrophobicity, charge and antibody subclass.
resultsIn the investigated conditions, the antibody aggregation follows a mechanism consisting of two-steps: reversible monomer oligomerization followed by irreversible cluster-cluster aggregation. The kinetics of the two steps is differently affected by the operating conditions: mild destabilizing conditions induce formation of oligomers which are stable within weeks, while stronger denaturing conditions promote aggregation of oligomers to larger aggregates which eventually precipitate. For different antibodies significant differences in both oligomerization and growth rates are found, even for antibodies belonging to the same subclass. For all antibodies the aggregate formation is accompanied by a structure re-organization with an increase in the ordered β-sheet structures. At low pH the aggregation propensity of the investigated antibodies does not correlate with antibody subclass, surface net charge and hydrophobicity of the non-native state.
conclusionsThe aggregation mechanism of three antibodies in acidic conditions as well as differences and analogies in their stability behavior has been characterized.
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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.