ArticleThe Journal of biological chemistry2013
Engineered soluble monomeric IgG1 CH3 domain: generation, mechanisms of function, and implications for design of biological therapeutics.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Label-Free Profiling of Immunoglobulin Isotypes Using Solid-State Nanopores.Small methods · 2026Article
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- Production of an Antibody Fragment (scFv) Targeting PcrV Protein of Pseudomonas aeruginosa in Fed-Batch Cultivation ModeIranian biomedical journal · 2021Article
- Characterization of a novel mCH3 conjugated anti-PcrV scFv molecule.Scientific reports · 2021Article
- The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology.Frontiers in plant science · 2021Article
- Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV.Antibodies (Basel, Switzerland) · 2019Article
- Comprehensive elucidation of the structural and functional roles of engineered disulfide bonds in antibody Fc fragment.The Journal of biological chemistry · 2018Article
- An explorative study towards the chemical synthesis of the immunoglobulin G1 Fc CH3 domain.Journal of peptide science : an official publication of the European Peptide Society · 2018Article
- HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions.Emerging microbes & infections · 2017Article
- Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds.Frontiers in immunology · 2017Review
- Engineered Soluble Monomeric IgG1 Fc with Significantly Decreased Non-Specific Binding.Frontiers in immunology · 2017Article
- Single-Domain Antibodies As Therapeutics against Human Viral Diseases.Frontiers in immunology · 2017Review
- Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.Frontiers in immunology · 2017Review
- Antibody Aggregation: Insights from Sequence and Structure.Antibodies (Basel, Switzerland) · 2016Review
- Engineered Autonomous Human Variable Domains.Current pharmaceutical design · 2016Review
- The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy.Advanced drug delivery reviews · 2015Review
- Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections.Microbes and infection · 2015Review
- Article
- Article
- Engineered Fc based antibody domains and fragments as novel scaffolds.Biochimica et biophysica acta · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Most of the therapeutic antibodies approved for clinical use are full-size IgG1 molecules. The interaction of the IgG1 Fc with the neonatal Fc receptor (FcRn) plays a critical role in maintaining their long half-life. We have hypothesized that isolated Fc domains could be engineered to functionally mimic full-size IgG1 (nanoantibodies) but with decreased (10-fold) size. Here, we report for the first time the successful generation of a soluble, monomeric CH3 domain (mCH3). In contrast to the wild-type dimeric CH3, the mCH3 exhibited pH-dependent binding to FcRn similar to that of Fc. The binding free energy of mCH3 to FcRn was higher than that of isolated CH2 but lower than that of Fc. Therefore, CH3 may contribute a larger portion of the free energy of binding to FcRn than CH2. A fusion protein of mCH3 with an engineered antibody domain (m36.4) also bound to FcRn in a pH-dependent fashion and exhibited significantly higher neutralizing activity against HIV-1 than m36.4-Fc fusion proteins. The m36.4-mCH3 fusion protein was monomeric, stable, soluble, and expressed at a high level in Escherichia coli. We also found that engineering an additional disulfide bond in mCH3 remarkably increased its thermal stability, whereas the FcRn binding was not affected. These data suggest that mCH3 could not only help in the exploration of the dual mechanisms of the CH3 contribution to Fc functions (dimerization and FcRn interactions) but could also be used for the development of candidate therapeutics with optimized half-life, enhanced tissue penetration, access to sterically restricted binding sites, and increased therapeutic efficacy.
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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.