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.

Th17 细胞产生的白细胞介素 17A (IL-17A) 通过刺激细胞因子和趋化因子的释放及其调节，促进各种自身免疫性疾病的发病机制。阻断IL-17A功能的抗IL-17A抗体已被证明是治疗自身免疫性疾病的有效方法。我们研究的目的是通过全面的体外和体内生物活性研究以及物理化学表征，产生一种潜在的人源化抗 IL-17A 治疗性单克隆抗体 (mAb)。HZD37-5是一种特异性识别IL-17A N78位点的人源化单克隆抗体，可与人和恒河猴结合，阻断IL-17诱导的信号转导和IL-6、IL-8、CXCL-1和G-GSF的释放. 在体内在小鼠模型中，HZD37-5 以剂量依赖性方式显着抑制人 IL-17A 诱导的角质形成细胞趋化因子 (KC) 分泌。HZD37-5在恒河猴体内的药代动力学（PK）研究结果表明，HZD37-5具有良好的PK特征，分布有限（78.0~78.8 ml/kg），消除缓慢（5.00~6.45 ml/day/kg），半长- 1.5 mg/kg 单次 IV 或 SC 剂量后的寿命（9.1-10.7 天）和高生物利用度（103%）。这些发现为 HZD37-5 提供了全面的临床前特征，并支持它可能被开发为治疗自身免疫性疾病的潜在疗法，包括银屑病、银屑病关节炎、中轴型脊柱关节炎等。