ArticleScientific reports2017
Multivalent Fcγ-receptor engagement by a hexameric Fc-fusion protein triggers Fcγ-receptor internalisation and modulation of Fcγ-receptor functions.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Structure-function analysis of the FCRL5-IgG1 Fc complex reveals an unappreciated pathway for B cell modulation by Fc-attenuated IgG.Science advances · 2026Article
- Structure-Function Analysis of the FCRL5-IgG1 Fc Complex Reveals an Unappreciated Effect of Fc-Silent Antibodies on B cells.bioRxiv : the preprint server for biology · 2026Article
- Molecular basis of CXC chemokine receptor 3 ligand multispecificity.Science advances · 2026Article
- Article
- Recombinant Human IgG1-Hexamer Reduces Pathogenic Autoantibodies in the K/BxN Mouse Model of Arthritis Independent of FcRn.International journal of molecular sciences · 2026Article
- Review
- An aptamer specifically targeting mCRP ameliorates experimental arthritis.Journal of orthopaedic translation · 2025Article
- Pre-Existing Anti-Vector Immunity to Adenovirus-Inspired VLP Vaccines Shows an Adjuvant-Dependent Antagonism.Vaccines · 2025Article
- Human Fc gamma receptor IIIA blockade inhibits platelet destruction in a humanized murine model of ITP.Blood advances · 2024Article
- Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors.Journal for immunotherapy of cancer · 2024Article
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
- FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis.Antibodies (Basel, Switzerland) · 2022Review
- Next-generation antibody-based therapies in neurology.Brain : a journal of neurology · 2022Review
- Review
- Engineering pan-HIV-1 neutralization potency through multispecific antibody avidity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Current therapeutic strategies and perspectives in refractory ITP: What have we learned recently?Frontiers in immunology · 2022Review
- Article
- Single-cell transcriptome identifiesiScience · 2021Article
- 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
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engagement of Fcγ-receptors triggers a range of downstream signalling events resulting in a diverse array of immune functions. As a result, blockade of Fc-mediated function is an important strategy for the control of several autoimmune and inflammatory conditions. We have generated a hexameric-Fc fusion protein (hexameric-Fc) and tested the consequences of multi-valent Fcγ-receptor engagement in in vitro and in vivo systems. In vitro engagement of hexameric-Fc with FcγRs showed complex binding interactions that altered with receptor density and triggered the internalisation and degradation of Fcγ-receptors. This caused a disruption of Fc-binding and phagocytosis. In vivo, in a mouse ITP model we observed a short half-life of hexameric-Fc but were nevertheless able to observe inhibition of platelet phagocytosis several days after hexameric-Fc dosing. In cynomolgus monkeys, we again observed a short half-life, but were able to demonstrate effective FcγR blockade. These findings demonstrate the ability of multi-valent Fc-based therapeutics to interfere with FcγR function and a potential mechanism through which they could have a sustained effect; the internalisation and degradation of FcγRs.
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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.