Therapeutic blockade of CXCR2 rapidly clears inflammation in arthritis and atopic dermatitis models: demonstration with surrogate and humanized antibodies
- Author(s)
- Alam, MJ; Xie, L; Ang, C; Fahimi, F; Willingham, SB; Kueh, AJ; Herold, MJ; Mackay, CR; Robert, R;
- Details
- Publication Year 2020,Volume 12,Issue #1,Page 1856460
- Journal Title
- MAbs
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- Taylor & Francis
- Keywords
- Cxcr2; arthritis; atopic Dermatitis; inflammation; neutrophil; therapeutic antibody
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 33347356
- Publisher's Version
- https://doi.org/10.1080/19420862.2020.1856460
- Open Access at Publisher's Site
https://doi.org/10.1080/19420862.2020.1856460- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:08:28
Last Modified: 2021-02-23 01:37:56