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Generation and Characterization of Ixekizumab, a Humanized Monoclonal Antibody That Neutralizes interleukin-17A

Generation and Characterization of Ixekizumab, a Humanized Monoclonal Antibody That Neutralizes interleukin-17A

Ling Liu, Jirong Lu, Barrett W Allan, Ying Tang, Jonathan Tetreault, Chi-Kin Chow, Barbra Barmettler, James Nelson, Holly Bina, Lihua Huang, Victor J Wroblewski, Kristine Kikly

J Inflamm Res. 2016 Apr 19;9:39-50.

PMID: 27143947

Abstract:

Interleukin (IL)-17A exists as a homodimer (A/A) or as a heterodimer (A/F) with IL-17F. IL-17A is expressed by a subset of T-cells, called Th17 cells, at inflammatory sites. Most cell types can respond to the local production of IL-17A because of the near ubiquitous expression of IL-17A receptors, IL-17RA and IL-17RC. IL-17A stimulates the release of cytokines and chemokines designed to recruit and activate both neutrophils and memory T-cells to the site of injury or inflammation and maintain a proinflammatory state. IL-17A-producing pathogenic T-cells contribute to the pathogenesis of autoimmune diseases, including psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. This study describes the generation and characterization of ixekizumab, a humanized IgG4 variant IL-17A-neutralizing antibody. Ixekizumab binds human and cynomolgus monkey IL-17A with high affinity and binds rabbit IL-17A weakly but does not bind to rodent IL-17A or other IL-17 family members. Ixekizumab effectively inhibits the interaction between IL-17A and its receptor in binding assays and potently blocks IL-17A-induced GRO or KC secretion in cell-based assays. In an in vivo mouse pharmcodynamic model, ixekizumab blocks human IL-17A-induced mouse KC secretion. These data provide a comprehensive preclinical characterization of ixekizumab, for which the efficacy and safety have been demonstrated in human clinical trials in psoriasis and psoriatic arthritis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416738	Anti-phospho-Caspase 9 (pSer196) antibody produced in rabbit			Price

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