ArticlemAbs2016
Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab.
Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 101 citations in OpenAlex.
- Simple Hydrodynamic Molecular Weight Model for Rapid Assessment of Therapeutic Protein Oligomerization States in Formulation.The AAPS journal · 2026Article
- CNS-compartmentalized IgG aggregates and glycosylation in multiple sclerosis contribute to oligoclonal bands and neuronal cytotoxicity.Frontiers in immunology · 2026Article
- Antibody glycosylation in neuroimmune diseases.Journal of translational medicine · 2025Review
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- Antigen-presenting cell internalization is key for understanding and evaluating therapeutic antibodies' immunogenicity.Frontiers in immunology · 2025Review
- A case study of a bispecific antibody manufacturability assessment and optimization during discovery stage and its implications.Antibody therapeutics · 2024Article
- Structural Characterization of a Pathogenic Antibody Underlying Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT).Analytical chemistry · 2024Article
- N-glycosylation as a eukaryotic protective mechanism against protein aggregation.Science advances · 2024Article
- Modulating antibody effector functions by Fc glycoengineering.Biotechnology advances · 2023Review
- Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide-Alkyne Cycloaddition Reactions.Pharmaceuticals (Basel, Switzerland) · 2023Article
- How can we discover developable antibody-based biotherapeutics?Frontiers in molecular biosciences · 2023Review
- Glycobiology of rheumatic diseases.Nature reviews. Rheumatology · 2023Review
- Non-specificity as the sticky problem in therapeutic antibody development.Nature reviews. Chemistry · 2022Review
- Protocols for Rational Design of Protein Solubility and Aggregation Properties Using Aggrescan3D Standalone.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Glycan Profile Analysis of Engineered Trastuzumab with Rationally Added Glycosylation Sequons Presents Significantly Increased Glycan Complexity.Pharmaceutics · 2021Article
- Peptide Inhibitors of Vascular Endothelial Growth Factor A: Current Situation and Perspectives.Pharmaceutics · 2021Review
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- A Rationally Designed Bovine IgA Fc Scaffold EnhancesFrontiers in plant science · 2021Article
- Immunoglobulin G Glycosylation in Diseases.Experientia supplementum (2012) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions.
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Registered trials
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.