ArticleThe Journal of biological chemistry2010
Kinetic approach to pathway attenuation using XOMA 052, a regulatory therapeutic antibody that modulates interleukin-1beta activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes.Diabetes care · 2012Trial
- Mechanotransduction Failure and Molecular Rescue in Gastric Cancer: Kinetotherapy Across the IL-6/STAT3-Myostatin/ACVR2B-Akt/mTOR Axis.Medical sciences (Basel, Switzerland) · 2026Review
- A Meta-Analysis Methodology in Stan to Estimate Population Pharmacokinetic Parameters from Multiple Aggregate Concentration-Time Datasets: Application to Gevokizumab mPBPK Model.Pharmaceutics · 2024Article
- Post-stroke inflammation-target or tool for therapy?Acta neuropathologica · 2019Review
- Effect of Gevokizumab on Interleukin-1β-Mediated Cytochrome P450 3A4 and Drug Transporter Repression in Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2017Article
- The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure.JACC. Basic to translational science · 2017Article
- Interleukin-1β-Targeted Vaccine Improves Glucose Control and β-Cell Function in a Diabetic KK-Ay Mouse Model.PloS one · 2016Article
- Novel Allosteric Modulators of G Protein-coupled Receptors.The Journal of biological chemistry · 2015Review
- Evasion of inflammasome activation by microbial pathogens.The Journal of clinical investigation · 2015Review
- International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.Pharmacological reviews · 2014Article
- Current approaches to fine mapping of antigen-antibody interactions.Immunology · 2014Review
- Selective allosteric antibodies to the insulin receptor for the treatment of hyperglycemic and hypoglycemic disorders.Journal of diabetes science and technology · 2014Article
- Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1β antibody with differential receptor-modulating properties.The Journal of pharmacology and experimental therapeutics · 2014Article
- Targeting interleukin-1 in heart disease.Circulation · 2013Review
- How biologics targeting the IL-1 system are being considered for the treatment of type 2 diabetes.British journal of clinical pharmacology · 2013Review
- Bridging Clinical Outcomes of Canakinumab Treatment in Patients With Rheumatoid Arthritis With a Population Model of IL-1β Kinetics.CPT: pharmacometrics & systems pharmacology · 2012Article
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- XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1β-mediated diseases.mAbsArticle
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many therapeutic antibodies act as antagonists to competitively block cellular signaling pathways. We describe here an approach for the therapeutic use of monoclonal antibodies based on context-dependent attenuation to reduce pathologically high activity while allowing homeostatic signaling in biologically important pathways. Such attenuation is achieved by modulating the kinetics of a ligand binding to its various receptors and regulatory proteins rather than by complete blockade of signaling pathways. The anti-interleukin-1beta (IL-1beta) antibody XOMA 052 is a potent inhibitor of IL-1beta activity that reduces the affinity of IL-1beta for its signaling receptor and co-receptor but not for its decoy and soluble inhibitory receptors. This mechanism shifts the effective dose response of the cytokine so that the potency of IL-1beta bound by XOMA 052 is 20-100-fold lower than that of IL-1beta in the absence of antibody in a variety of in vitro cell-based assays. We propose that by decreasing potency of IL-1beta while allowing binding to its clearance and inhibitory receptors, XOMA 052 treatment will attenuate IL-1beta activity in concert with endogenous regulatory mechanisms. Furthermore, the ability to bind the decoy receptor may reduce the potential for accumulation of antibody.target complexes. Regulatory antibodies like XOMA 052, which selectively modulate signaling pathways, may represent a new mechanistic class of therapeutic antibodies.
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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.