ArticleThe Journal of biological chemistry2017
Targeted Fcγ Receptor (FcγR)-mediated Clearance by a Biparatopic Bispecific Antibody.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention.PLoS computational biology · 2022Pooled it
- Analytical Ultracentrifugation for Biopharmaceutical Characterization and Quality Control.International journal of molecular sciences · 2026Review
- Modified Anti-PstS1 Bi-specific antibodies unlock potent protection against tuberculosis.PLoS pathogens · 2026Article
- Albumin Levels Are Predictive of Cachexia-Induced Time-Dependent Clearance of Therapeutic Antibodies: A Physiologically Based Pharmacokinetic Model of Durvalumab.CPT: pharmacometrics & systems pharmacology · 2026Article
- Multimodal Physicochemical Characterization of Cross-Linking Activities of Biparatopic Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- PET imaging of Aspergillus infection using Zirconium-89 labeled anti-β-glucan antibody fragments.European journal of nuclear medicine and molecular imaging · 2024Article
- Decoupling FcRn and tumor contributions to elevated immune checkpoint inhibitor clearance in cancer cachexia.Pharmacological research · 2024Article
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.Pharmacology & therapeutics · 2022Review
- Plasma cell biology: Foundations for targeted therapeutic development in transplantation.Immunological reviews · 2021Review
- Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice.iScience · 2021Article
- Live Imaging of Innate and Adaptive Immune Responses in the Liver.Frontiers in immunology · 2020Review
- Expeditious Generation of Biparatopic Common Light Chain AntibodiesFrontiers in immunology · 2020Article
- An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.Nature communications · 2019Article
- Sensitivity of Kupffer cells and liver sinusoidal endothelial cells to ricin toxin and ricin toxin-Ab complexes.Journal of leukocyte biology · 2019Article
- Multiple Variables at the Leukocyte Cell Surface Impact Fc γ Receptor-Dependent Mechanisms.Frontiers in immunology · 2019Review
- Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients.Antibodies (Basel, Switzerland) · 2019Review
- Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018Review
- Structural insights into the mechanism of action of a biparatopic anti-HER2 antibody.The Journal of biological chemistry · 2018Article
- Factors Affecting the Pharmacology of Antibody-Drug Conjugates.Antibodies (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble ligands have commonly been targeted by antibody therapeutics for cancers and other diseases. Although monoclonal antibodies targeting such ligands can block their interactions with their cognate receptors, they can also significantly increase the half-life of their ligands by FcRn-mediated antibody recycling, thereby evading ligand renal clearance and requiring increasingly high antibody doses to neutralize the increasing pool of target. To overcome this issue, we generated a bispecific/biparatopic antibody (BiSAb) that targets two different epitopes on IL-6 to block IL-6-mediated signaling. The BiSAb formed large immune complexes with IL-6 that can bind Fcγ receptors on phagocytic cells and are rapidly internalized. In addition, rapid clearance of the BiSAb·IL-6 complex was observed in mice while the parental antibodies prolonged the serum half-life of IL-6. Intravital imaging of the liver in mice confirmed that the rapid clearance of these large immune complexes was associated with Fcγ receptor-dependent binding to Kupffer cells in the liver. The approach described here provides a general strategy for therapeutic antibodies with the ability to not only neutralize but also actively drive clearance of their soluble antigens.
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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.