ArticleCommunications biology2021
On-target IgG hexamerisation driven by a C-terminal IgM tail-piece fusion variant confers augmented complement activation.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed.
- Combination of Fc-Protein Engineering Strategies: Design and Evaluation of Antibody Effector Functions.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Pre-clinical efficacy of a C4BP hexameric IgG Fc fusion protein against Neisseria gonorrhoeae.PloS one · 2026Article
- Review
- Article
- Isotype conversion of Staphylococcal-specific IgG into IgM broadens the reactivity to other bacterial pathogens.Cell reports. Medicine · 2025Article
- Neutralizing Antibodies vs. Viruses: Interacting Mechanisms and Escape Tactics.Microorganisms · 2025Review
- Antibody dependent complement activation is critical for boosting opsonophagocytosis of Staphylococcus epidermidis in an extremely preterm human whole blood model.Scientific reports · 2025Article
- Preparation of Monoclonal Antibodies Against the gD Protein of Feline Herpesvirus Type-1 by mRNA Immunization.Veterinary sciences · 2025Article
- Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance.International journal of molecular sciences · 2024Review
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
- Unlocking the Power of Complement-Dependent Cytotoxicity: Engineering Strategies for the Development of Potent Therapeutic Antibodies for Cancer Treatments.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Article
- Innovations in monoclonal antibody-based multipurpose prevention technology (MPT) for the prevention of sexually transmitted infections and unintended pregnancy.Frontiers in reproductive health · 2023Review
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Multivalent ACE2 engineering-A promising pathway for advanced coronavirus nanomedicine development.Nano today · 2022Review
- Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections.Biomedicines · 2022Review
- Dual Fc optimization to increase the cytotoxic activity of a CD19-targeting antibody.Frontiers in immunology · 2022Article
- Sialylation as an Important Regulator of Antibody Function.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The majority of depleting monoclonal antibody (mAb) drugs elicit responses via Fc-FcγR and Fc-C1q interactions. Optimal C1q interaction is achieved through hexameric Fc:Fc interactions at the target cell surface. Herein is described an approach to exploit the tailpiece of the naturally multimeric IgM to augment hexamerisation of IgG. Fusion of the C-terminal tailpiece of IgM promoted spontaneous hIgG hexamer formation, resulting in enhanced C1q recruitment and complement-dependent cytotoxicity (CDC) but with off-target complement activation and reduced in-vivo efficacy. Mutation of the penultimate tailpiece cysteine to serine (C575S) ablated spontaneous hexamer formation, but facilitated reversible hexamer formation after concentration in solution. C575S mutant tailpiece antibodies displayed increased complement activity only after target binding, in-line with the concept of 'on-target hexamerisation', whilst retaining efficient in-vivo efficacy and augmented target cell killing in the lymph node. Hence, C575S-tailpiece technology represents an alternative format for promoting on-target hexamerisation and enhanced CDC.
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Registered trials
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