ArticleProtein engineering, design & selection : PEDS2013
Engineered antibody Fc variant with selectively enhanced FcγRIIb binding over both FcγRIIa(R131) and FcγRIIa(H131).
Article in Protein engineering, design & selection : PEDS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 80 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
80 citing papers in PubMed, 128 citations in OpenAlex.
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote antitumor immunity.Nature cancer · 2026Article
- IMGT-NC Engineered Variants of INN Therapeutic IG or Antibodies and Related IgSF Proteins (TR, FPIA and CPCA): Bridging Sequences, Structures and Functions for AI.Biomolecules · 2026Review
- Mouse Fc-FcγRIV structure guides Fc engineering for cross-species FcγR recognition.bioRxiv : the preprint server for biology · 2026Article
- ROSE12, a novel anti-CTLA-4 FcγRs binding-enhanced antibody activated by extracellular adenosine triphosphate, shows tumor-selective regulatory T-cell depletion and antitumor efficacy without systemic immune activation.Journal for immunotherapy of cancer · 2026Article
- Human FcRL5 is an Fc receptor that simultaneously engages two IgGs.Science advances · 2026Article
- Harnessing multivalency and FcγRIIB engagement to augment anti-CD27 immunotherapy.Nature communications · 2025Article
- Chimeras co-targeting antigens and FcγRIIb trigger degradation of extracellular soluble proteins and pathological aggregates.Nature communications · 2025Article
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- The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors.Science (New York, N.Y.) · 2025Article
- FcγRI is the key determinant of antibody-mediated Zika virus infection of human placental macrophages.bioRxiv : the preprint server for biology · 2025Article
- A Comprehensive Review of Fc Gamma Receptors and Their Role in Systemic Lupus Erythematosus.International journal of molecular sciences · 2025Review
- Towards a unifying model for B-cell receptor triggering.Nature reviews. Immunology · 2025Review
- CD32B1, a versatile non-signaling antibody-binding scaffold for enhanced T cell adhesion to tumor stromal cognate antigens.Frontiers in immunology · 2025Article
- Cross-species analysis of FcγRIIa/b (CD32a/b) polymorphisms at position 131: structural and functional insights into the mechanism of IgG- mediated phagocytosis in human and macaque.Frontiers in immunology · 2025Article
- 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
- Systematic Preparation of a 66-IgG Library with Symmetric and Asymmetric Homogeneous Glycans and Their Functional Evaluation.Journal of the American Chemical Society · 2024Article
- Fc engineering by monoclonal mammalian cell display for improved affinity and selectivity towards FcγRs.Antibody therapeutics · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engaging inhibitory FcγRIIb by Fc region has been recently reported to be an attractive approach for improving the efficacy of antibody therapeutics. However, the previously reported S267E/L328F variant with enhanced binding affinity to FcγRIIb, also enhances binding affinity to FcγRIIa(R131) allotype to a similar degree because FcγRIIb and FcγRIIa(R131) are structurally similar. In this study, we applied comprehensive mutagenesis and structure-guided design based on the crystal structure of the Fc/FcγRIIb complex to identify a novel Fc variant with selectively enhanced FcγRIIb binding over both FcγRIIa(R131) and FcγRIIa(H131). This novel variant has more than 200-fold stronger binding affinity to FcγRIIb than wild-type IgG1, while binding affinity to FcγRIIa(R131) and FcγRIIa(H131) is comparable with or lower than wild-type IgG1. This selectivity was achieved by conformational change of the C(H)2 domain by mutating Pro to Asp at position 238. Fc variant with increased binding to both FcγRIIb and FcγRIIa induced platelet aggregation and activation in an immune complex form in vitro while our novel variant did not. When applied to agonistic anti-CD137 IgG1 antibody, our variant greatly enhanced the agonistic activity. Thus, the selective enhancement of FcγRIIb binding achieved by our Fc variant provides a novel tool for improving the efficacy of antibody therapeutics.
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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.