ArticlemAbs2017
Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.
Article in mAbs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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
19 citing papers in PubMed, 31 citations in OpenAlex.
- CSL305: A Dual Functional Therapeutic Antibody Targeting Complement C2 and FcRn.International journal of molecular sciences · 2026Article
- Effect of FcRn Binding on Monoclonal Antibody Disposition in the Brain.The AAPS journal · 2025Article
- Single-Batch Expression of an Experimental Recombinant Snakebite Antivenom Based on an Oligoclonal Mixture of Human Monoclonal Antibodies.Biotechnology journal · 2024Article
- Clinical efficacy and safety of switching from eculizumab to ravulizumab in adult patients with aHUS- real-world data.BMC nephrology · 2024Article
- Phage display assisted discovery of a pH-dependent anti-α-cobratoxin antibody from a natural variable domain library.Protein science : a publication of the Protein Society · 2023Article
- Mechanistic incorporation of FcRn binding in plasma and endosomes in a whole body PBPK model for large molecules.Journal of pharmacokinetics and pharmacodynamics · 2023Article
- Impact of structural modifications of IgG antibodies on effector functions.Frontiers in immunology · 2023Review
- Non-specificity as the sticky problem in therapeutic antibody development.Nature reviews. Chemistry · 2022Review
- Monoclonal Antibody Engineering and Design to Modulate FcRn Activities: A Comprehensive Review.International journal of molecular sciences · 2022Review
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Algorithmic multiscale analysis for the FcRn mediated regulation of antibody PK in human.Scientific reports · 2022Article
- Antibody variable sequences have a pronounced effect on cellular transport and plasma half-life.iScience · 2022Article
- Yeast Display Guided Selection of pH-Dependent Binders.Methods in molecular biology (Clifton, N.J.) · 2022Article
- In Translation: FcRn across the Therapeutic Spectrum.International journal of molecular sciences · 2021Review
- pH-responsive antibodies for therapeutic applications.Journal of biomedical science · 2021Review
- Targeting FcRn to Generate Antibody-Based Therapeutics.Trends in pharmacological sciences · 2018Review
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Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.
Indexed as
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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.