1. Generation and characterization of a humanized anti-IL-17A rabbit monoclonal antibody
- Author
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Yi Zhou, Meijuan Wu, Wu Yiliang, Qiu Jiwan, Qiu Zhihua, Li Wang, Chen Wei, Kong Yong, Chen Tao, and Qiao Huaiyao
- Subjects
Keratinocytes ,Chemokine ,medicine.drug_class ,Chemokine CXCL1 ,Pharmacology ,Monoclonal antibody ,Antibodies, Monoclonal, Humanized ,Autoimmune Diseases ,Mice ,Pharmacokinetics ,In vivo ,medicine ,Animals ,Humans ,Autoimmune disease ,biology ,Chemotactic Factors ,Dose-Response Relationship, Drug ,business.industry ,Interleukin-6 ,Interleukin-17 ,Interleukin-8 ,Biological activity ,medicine.disease ,Macaca mulatta ,In vitro ,biology.protein ,Rabbits ,Antibody ,business ,Biotechnology ,Signal Transduction - Abstract
Interleukin-17A (IL-17A) produced by Th17 cells, contributes to the pathogenesis of various autoimmune diseases by stimulating the release of cytokines and chemokines and its regulation. Anti-IL-17A antibody which blocks the function of IL-17A has been proved to be an effective treatment of autoimmune disease. The aim of our study was to generate a potential humanized anti-IL-17A therapeutic monoclonal antibody (mAb) through a comprehensive panel of in vitro and in vivo biological activity studies, as well as physicochemical characterization. HZD37-5, a humanized monoclonal antibody specifically recognizing N78 loci of IL-17A, binds to human and rhesus monkeys, blocks IL-17 induced signal transduction and the release of IL-6, IL-8, CXCL-1 and G-GSF. In an in vivo efficacy mouse model, HZD37-5 significantly inhibited human IL-17A induced-keratinocyte chemoattractant (KC) secretion in a dose-dependent manner. The pharmacokinetics (PK) study result of HZD37-5 in rhesus monkeys indicated that HZD37-5 had favorable PK characteristics with limited distribution (78.0–78.8 ml/kg), slow elimination (5.00–6.45 ml/day/kg), long half-life (9.1–10.7 days) and high bioavailability (103%) following a single IV or SC dose at 1.5 mg/kg. These findings provided a comprehensive preclinical characterization of HZD37-5 and supported that it may be developed as a potential therapeutic for the treatment of autoimmune diseases, including psoriasis, psoriatic arthritis, axial spondyloarthritis, etc.
- Published
- 2021