ArticleAntibodies (Basel, Switzerland)2017
Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality.
Article in Antibodies (Basel, Switzerland), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Efficacy and safety of serplulimab in solid tumors: a meta-analysis.Frontiers in pharmacology · 2025Pooled it
- 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
- Structure-function analysis of the FCRL5-IgG1 Fc complex reveals an unappreciated pathway for B cell modulation by Fc-attenuated IgG.Science advances · 2026Article
- Myeloid cell-mediated killing of B-ALL by CD38 and CD20 IgA antibody variants is enhanced by CD47/SIRPα interference.Blood neoplasia · 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
- Development and Humanization of a Camelid-Derived Neutralizing Nanobody Targeting Botulinum Neurotoxin Type A.International journal of nanomedicine · 2026Article
- Role of TPD52 in Endometrial Cancer: Impact on EMT and the PI3K/AKT and ERK/MAPK Signaling.Protein and peptide letters · 2025Article
- Using atomistic solution scattering modelling to elucidate the role of the Fc glycans in human IgG4.PloS one · 2024Article
- Profiling the Biophysical Developability Properties of Common IgG1 Fc Effector Silencing Variants.Antibodies (Basel, Switzerland) · 2023Article
- Mutation of the TGN1412 anti-CD28 monoclonal antibody lower hinge confers specific FcγRIIb binding and retention of super-agonist activity.Immunology and cell biology · 2023Article
- Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer.Frontiers in immunology · 2023Review
- Impact of structural modifications of IgG antibodies on effector functions.Frontiers in immunology · 2023Review
- Long-Duration and Non-Invasive Photoacoustic Imaging of Multiple Anatomical Structures in a Live Mouse Using a Single Contrast Agent.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Dual Fc optimization to increase the cytotoxic activity of a CD19-targeting antibody.Frontiers in immunology · 2022Article
- Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent phagocytosis of lymphoma cells by macrophages.Frontiers in immunology · 2022Article
- Optimized Production of Fc Fusion Proteins by Sortase Enzymatic Ligation.Industrial & engineering chemistry research · 2021Article
- A Strategy for Selective Deletion of Autoimmunity-Related T Cells by pMHC-Targeted Delivery.Pharmaceutics · 2021Article
- Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases.Cellular & molecular immunology · 2021Article
- Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy.PloS one · 2021Article
- Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcγ) receptor-expressing immune cells. We previously reported on a human IgG2 variant termed IgG2σ with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and Fcγ receptor binding assays. Here, we extend that work to IgG1 and IgG4 antibodies, alternative subtypes which may offer advantages over IgG2 antibodies. In several in vitro and in vivo assays, the IgG1σ and IgG4σ variants showed equal or even lower Fc-related activities than the corresponding IgG2σ variant. In particular, IgG1σ and IgG4σ variants demonstrate complete lack of effector function as measured by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and in vivo T-cell activation. The IgG1σ and IgG4σ variants showed acceptable solubility and stability, and typical human IgG1 pharmacokinetic profiles in human FcRn-transgenic mice and cynomolgus monkeys. In silico T-cell epitope analyses predict a lack of immunogenicity in humans. Finally, crystal structures and simulations of the IgG1σ and IgG4σ Fc domains can explain the lack of Fc-mediated immune functions. These variants show promise for use in those therapeutic antibodies and Fc fusions for which the Fc domain should be immunologically "silent".
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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.