ArticlemAbs
Engineering a therapeutic IgG molecule to address cysteinylation, aggregation and enhance thermal stability and expression.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- Humanized mice enableMolecular therapy. Advances · 2026Article
- Evaluation of "Difficult-to-Express" Monoclonal Antibodies in a CHO-Based Hybrid Site-Specific Integration System Under Industrially Relevant Conditions.Biotechnology journal · 2025Article
- Introduction of Reactive Thiol Handles into Tyrosine-Tagged Proteins through Enzymatic Oxidative Coupling.Journal of the American Chemical Society · 2025Article
- From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems.International journal of molecular sciences · 2025Review
- Development of a Novel Label-Free Subunit HILIC-MS Method for Domain-Specific Free Thiol Identification and Quantitation in Therapeutic Monoclonal Antibodies.Journal of the American Society for Mass Spectrometry · 2024Article
- Stability of Protein Pharmaceuticals: Recent Advances.Pharmaceutical research · 2024Review
- LAP: Liability Antibody Profiler by sequence & structural mapping of natural and therapeutic antibodies.PLoS computational biology · 2024Article
- Effect of Free Cysteine Residues to Serine Mutation on Cellodextrin Phosphorylase.Journal of applied glycoscience · 2024Article
- Developability assessment at early-stage discovery to enable development of antibody-derived therapeutics.Antibody therapeutics · 2023Review
- Fortuitous Somatic Mutations during Antibody Evolution Endow Broad Neutralization against SARS-CoV-2 Omicron Variants.bioRxiv : the preprint server for biology · 2022Article
- Antibody stabilization for thermally accelerated deep immunostaining.Nature methods · 2022Article
- Recombinant antibodies aggregation and overcoming strategies in CHO cells.Applied microbiology and biotechnology · 2022Review
- A Review of Methodologies for the Detection, Quantitation, and Localization of Free Cysteine in Recombinant Proteins: A Focus on Therapeutic Monoclonal Antibodies.Frontiers in molecular biosciences · 2022Review
- In-solution buffer-free digestion allows full-sequence coverage and complete characterization of post-translational modifications of the receptor-binding domain of SARS-CoV-2 in a single ESI-MS spectrum.Analytical and bioanalytical chemistry · 2021Article
- A Rationally Designed Bovine IgA Fc Scaffold EnhancesFrontiers in plant science · 2021Article
- Expression vector cassette engineering for recombinant therapeutic production in mammalian cell systems.Applied microbiology and biotechnology · 2020Review
- Framework Mutations of the 10-1074 bnAb Increase Conformational Stability, Manufacturability, and Stability While Preserving Full Neutralization Activity.Journal of pharmaceutical sciences · 2020Article
- Comparative structural and thermal stability studies of Cuc m 2.0101, Art v 4.0101 and other allergenic profilins.Molecular immunology · 2019Article
- Optimization of an Antibody Light Chain Framework Enhances Expression, Biophysical Properties and Pharmacokinetics.Antibodies (Basel, Switzerland) · 2019Article
- Macro- and Micro-Heterogeneity of Natural and Recombinant IgG Antibodies.Antibodies (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibodies can undergo a variety of covalent and non-covalent degradation reactions that have adverse effects on efficacy, safety, manufacture and storage. We had identified an antibody to Angiopoietin 2 (Ang2 mAb) that neutralizes Ang2 binding to its receptor in vitro and inhibits tumor growth in vivo. Despite favorable pharmacological activity, the Ang2 mAb preparations were heterogeneous, aggregated rapidly and were poorly expressed. Here, we report the engineering of the antibody variable and constant domains to generate an antibody with reduced propensity to aggregate, enhanced homogeneity, 11°C elevated T(m), 26-fold improved level of expression and retained activity. The engineered molecule, MEDI-3617, is now compatible with the large scale material supply required for clinical trials and is currently being evaluated in Phase 1 in cancer patients. This is the first report to describe the stability engineering of a therapeutic antibody addressing non canonical cysteine residues and the design strategy reported here is generally applicable to other therapeutic antibodies and proteins.
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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.