Therapeutic blockade of CXCR2 rapidly clears inflammation in arthritis and atopic dermatitis models: demonstration with surrogate and humanized antibodies
Autor: | Liang Xie, Jahangir Alam, Farnaz Fahimi, Charles R. Mackay, Caroline Ang, Marco J Herold, Andrew J. Kueh, Remy Robert, Stephen B. Willingham |
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Rok vydání: | 2020 |
Předmět: |
medicine.drug_class
Immunology Arthritis Mice Transgenic Inflammation Antibodies Monoclonal Humanized Monoclonal antibody Receptors Interleukin-8B Dermatitis Atopic Mice 03 medical and health sciences Chemokine receptor 0302 clinical medicine Report Animals Immunology and Allergy Medicine Neutrophil homeostasis 030304 developmental biology 0303 health sciences CXCR2 Innate immune system business.industry neutrophil Atopic dermatitis medicine.disease Arthritis Experimental atopic Dermatitis arthritis inflammation therapeutic antibody 030220 oncology & carcinogenesis Chronic inflammatory response Female medicine.symptom business |
Zdroj: | mAbs article-version (VoR) Version of Record |
ISSN: | 1942-0870 1942-0862 |
Popis: | Neutrophils are the most abundant effector cells of the innate immune system and represent the first line of defense against infection. However, in many common pathologies, including autoimmune diseases, excessive recruitment and activation of neutrophils can drive a chronic inflammatory response leading to unwanted tissue destruction. Several strategies have been investigated to tackle pathologic neutrophil biology, and thus provide a novel therapy for chronic inflammatory diseases. The chemokine receptor CXCR2 plays a crucial role in regulating neutrophil homeostasis and is a promising pharmaceutical target. In this study, we report the discovery and validation of a humanized anti-human CXCR2 monoclonal antibody. To enable in vivo studies, we developed a surrogate anti-mouse CXCR2 antibody, as well as a human knock-in CXCR2 mouse. When administered in models of atopic dermatitis (AD) and rheumatoid arthritis (RA), the antibodies rapidly clear inflammation. Our findings support further developments of anti-CXCR2 mAb approaches not only for RA and AD, but also for other neutrophil-mediated inflammatory conditions where neutrophils are pathogenic and medical needs are unmet. |
Databáze: | OpenAIRE |
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