ArticleScientific reports2016
Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 121 citations in OpenAlex.
- Prediction of antibody non-specificity using protein language models and biophysical parameters.mAbs · 2026Article
- The Evolution of Artificial Intelligence in Antibody Design: From Structure-Based Engineering to Generative Models.Antibodies (Basel, Switzerland) · 2026Review
- Glycosylation-modulated conformational diversity in neurotrophin receptors.Biophysical journal · 2026Article
- Bridging Inflammation and Oncology: The Role and Therapeutic Potential of Macrophage Migration Inhibitory Factor in Lung Cancer.International journal of molecular sciences · 2026Review
- Against All Odds: Computational Screening Via Machine Learning Ranking and Generation of Antibody Candidates for Creutzfeldt-Jakob Disease.microPublication biology · 2026Article
- Ultra-Dilute Developability Analysis of Antibody Self-Association and Non-Specific Binding.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Antibody Affinity Maturation by Computational Design.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Article
- Article
- Developing high-concentration monoclonal antibody formulations for subcutaneous administration to improve patient treatment.Biophysical reviews · 2025Review
- Rationalizing mAb Candidate Screening Using a Single Holistic Developability Parameter.Molecular pharmaceutics · 2025Article
- Optimising Monoclonal Antibody Drug Development for Inflammatory Bowel Disease.Clinical and experimental gastroenterology · 2025Review
- Directed evolution of drug-like Aβ conformation-specific antibodies.Frontiers in immunology · 2025Article
- Integrating In Silico and In Vitro Tools for Optimized Antibody Development-Design of Therapeutic Anti-oxMIF Antibodies.Antibodies (Basel, Switzerland) · 2024Article
- Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions.Cell reports · 2024Article
- Aggrescan4D: A comprehensive tool for pH-dependent analysis and engineering of protein aggregation propensity.Protein science : a publication of the Protein Society · 2024Review
- DOTAD: A Database of Therapeutic Antibody Developability.Interdisciplinary sciences, computational life sciences · 2024Article
- Protein language models enable prediction of polyreactivity of monospecific, bispecific, and heavy-chain-only antibodies.Antibody therapeutics · 2024Article
- Understanding the Specific Implications of Amino Acids in the Antibody Development.The protein journal · 2024Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 3 institutions in 2 countries.
Funding
Abstract
Uncontrolled self-association is a major challenge in the exploitation of proteins as therapeutics. Here we describe the development of a structural proteomics approach to identify the amino acids responsible for aberrant self-association of monoclonal antibodies and the design of a variant with reduced aggregation and increased serum persistence in vivo. We show that the human monoclonal antibody, MEDI1912, selected against nerve growth factor binds with picomolar affinity, but undergoes reversible self-association and has a poor pharmacokinetic profile in both rat and cynomolgus monkeys. Using hydrogen/deuterium exchange and cross-linking-mass spectrometry we map the residues responsible for self-association of MEDI1912 and show that disruption of the self-interaction interface by three mutations enhances its biophysical properties and serum persistence, whilst maintaining high affinity and potency. Immunohistochemistry suggests that this is achieved via reduction of non-specific tissue binding. The strategy developed represents a powerful and generic approach to improve the properties of therapeutic proteins.
Indexed as
Identifiers
What OpenQuestion holds
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.