ArticleCommunications biology2018
Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions.
Article in Communications biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Mouse Fc-FcγRIV structure guides Fc engineering for cross-species FcγR recognition.bioRxiv : the preprint server for biology · 2026Article
- Review
- The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk.PLoS genetics · 2025Article
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.The Journal of clinical investigation · 2022Article
- Review
- Current therapeutic strategies and perspectives in refractory ITP: What have we learned recently?Frontiers in immunology · 2022Review
- On-target IgG hexamerisation driven by a C-terminal IgM tail-piece fusion variant confers augmented complement activation.Communications biology · 2021Article
- Dendritic Cell Tumor Vaccination via Fc Gamma Receptor Targeting: Lessons Learned from Pre-Clinical and Translational Studies.Vaccines · 2021Review
- Designed proteins assemble antibodies into modular nanocages.Science (New York, N.Y.) · 2021Article
- The Dual Targeting of FcRn and FcγRsFrontiers in immunology · 2021Article
- Designed proteins assemble antibodies into modular nanocages.bioRxiv : the preprint server for biology · 2020Article
- Antibody Structure and Function: The Basis for Engineering Therapeutics.Antibodies (Basel, Switzerland) · 2019Review
- Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms.Frontiers in immunology · 2019Review
- The Emerging Role of Complement Proteins as a Target for Therapy of IgA Nephropathy.Frontiers in immunology · 2019Review
- Impact of Human FcγR Gene Polymorphisms on IgG-Triggered Cytokine Release: Critical Importance of Cell Assay Format.Frontiers in immunology · 2019Article
- Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoantibody-mediated diseases are currently treated with intravenous immunoglobulin, which is thought to act in part via blockade of Fc gamma receptors, thereby inhibiting autoantibody effector functions and subsequent pathology. We aimed to develop recombinant molecules with enhanced Fc receptor avidity and thus increased potency over intravenous immunoglobulin. Here we describe the molecular engineering of human Fc hexamers and explore their therapeutic and safety profiles. We show Fc hexamers were more potent than IVIG in phagocytosis blockade and disease models. However, in human whole-blood safety assays incubation with IgG1 isotype Fc hexamers resulted in cytokine release, platelet and complement activation, whereas the IgG4 version did not. We used a statistically designed mutagenesis approach to identify the key Fc residues involved in these processes. Cytokine release was found to be dependent on neutrophil FcγRIIIb interactions with L234 and A327 in the Fc. Therefore, Fc hexamers provide unique insights into Fc receptor biology.
Identifiers
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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.