ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Inhibitory FcγRIIb-Mediated Soluble Antigen Clearance from Plasma by a pH-Dependent Antigen-Binding Antibody and Its Enhancement by Fc Engineering.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Engineering Antibodies into Targeted Chimeras: From Recognition Modules to Programmable Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A cytokine receptor-targeting chimera toolbox for expanding extracellular targeted protein degradation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Treatment strategies for rituximab-resistant primary membranous nephropathy: from resistance mechanisms to emerging therapies.Frontiers in immunology · 2026Review
- Chimeras co-targeting antigens and FcγRIIb trigger degradation of extracellular soluble proteins and pathological aggregates.Nature communications · 2025Article
- Review
- A cytokine receptor-targeting chimera (kineTAC) toolbox for expanding extracellular targeted protein degradation.bioRxiv : the preprint server for biology · 2025Article
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcγRIIb binding.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- A Dual-domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Extracellular targeted protein degradation: an emerging modality for drug discovery.Nature reviews. Drug discovery · 2024Review
- Two in one: the emerging concept of bifunctional antibodies.Current opinion in biotechnology · 2024Review
- Rapid Generation of Murine Bispecific Antibodies Using FAST-IgAntibodies (Basel, Switzerland) · 2024Article
- Impact of structural modifications of IgG antibodies on effector functions.Frontiers in immunology · 2023Review
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Improving Antibody Therapeutics by Manipulating the Fc Domain: Immunological and Structural Considerations.Annual review of biomedical engineering · 2022Review
- Strategies Towards Antigen-Specific Treatments for Membranous Nephropathy.Frontiers in immunology · 2022Review
- A cell based assay for evaluating binding and uptake of an antibody using hepatic nonparenchymal cells.Scientific reports · 2021Article
- Novel myostatin-specific antibody enhances muscle strength in muscle disease models.Scientific reports · 2021Article
- pH-responsive antibodies for therapeutic applications.Journal of biomedical science · 2021Review
- Tetravalent Bispecific Tandem Antibodies Improve Brain Exposure and Efficacy in an Amyloid Transgenic Mouse Model.Molecular therapy. Methods & clinical development · 2020Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fc engineering can modulate the Fc-FcγR interaction and thus enhance the potency of Abs that target membrane-bound Ags, but it has not been applied to Abs that target soluble Ags. In this study, we revealed a previously unknown function of inhibitory FcγRII in vivo and, using an Ab that binds to Ag pH dependently, demonstrated that the function can be exploited to target soluble Ag. Because pH-dependent Ab dissociates Ag in acidic endosome, its Ag clearance from circulation reflects the cellular uptake rate of Ag/Ab complexes. In vivo studies showed that FcγR but not neonatal FcR contributes to Ag clearance by the pH-dependent Ab, and when Fc binding to mouse FcγRII and III was increased, Ag clearance was markedly accelerated in wild-type mice and FcR γ-chain knockout mice, but the effect was diminished in FcγRII knockout mice. This demonstrates that mouse FcγRII efficiently promotes Ab uptake into the cell and its subsequent recycling back to the cell surface. Furthermore, when a human IgG1 Fc variant with selectively increased binding to human FcγRIIb was tested in human FcγRIIb transgenic mice, Ag clearance was accelerated without compromising the Ab half-life. Taken together, inhibitory FcγRIIb was found to play a prominent role in the cellular uptake of monomeric Ag/Ab immune complexes in vivo, and when the Fc of a pH-dependent Ab was engineered to selectively enhance human FcγRIIb binding, the Ab could accelerate soluble Ag clearance from circulation. We assume such a function would enhance the therapeutic potency of Abs that target soluble Ags.
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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.