State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Genrix (Shanghai) Biopharmaceutical Co., Ltd, Shanghai, China.
Biochem Biophys Res Commun. 2019 Sep 17;517(2):303-309. doi: 10.1016/j.bbrc.2019.07.078. Epub 2019 Jul 25.
Interleukin-17A (IL-17A) is a soluble pro-inflammatory cytokine, which is mainly secreted by Th17 cells. In humans, IL-17A mRNA and protein levels are increased in several autoimmune diseases, including psoriasis and rheumatoid arthritis. This study describes the preclinical in vitro and in vivo characterization of GR1501, a human IL-17A-neutralizing IgG4 monoclonal antibody. GR1501 binds human, rhesus and cynomolgus IL-17A with high affinity but does not bind to mouse IL-17A or other IL-17 family members. GR1501 effectively blocks the interaction between IL-17A and its receptor IL-17RA, thereby inhibiting IL-17A-induced CXCL1 and IL-6 release in cells and mice. In mouse air pouch model, GR1501 effectively inhibits IL-17A induced leukocytes infiltration into the air pouch. GR1501 also reduces joint swelling and inflammation in mouse arthritis model. These data suggest that GR1501 is a potent and selective IL-17A-neutralizing monoclonal antibody and will support the clinical investigation of this monoclonal antibody in psoriasis and rheumatoid arthritis.
白细胞介素-17A（IL-17A）是一种可溶性促炎细胞因子，主要由 Th17 细胞分泌。在人类中，几种自身免疫性疾病（包括银屑病和类风湿关节炎）中 IL-17A 的 mRNA 和蛋白水平增加。本研究描述了 GR1501 的临床前体外和体内特征，GR1501 是一种人源 IL-17A 中和 IgG4 单克隆抗体。GR1501 与人、恒河猴和食蟹猴的 IL-17A 具有高亲和力，但不与鼠 IL-17A 或其他 IL-17 家族成员结合。GR1501 可有效阻断 IL-17A 与其受体 IL-17RA 之间的相互作用，从而抑制细胞和小鼠中 IL-17A 诱导的 CXCL1 和 IL-6 释放。在小鼠气囊模型中，GR1501 可有效抑制 IL-17A 诱导的白细胞浸润到气囊中。GR1501 还可减少小鼠关节炎模型中的关节肿胀和炎症。这些数据表明，GR1501 是一种有效的、选择性的 IL-17A 中和单克隆抗体，并将支持该单克隆抗体在银屑病和类风湿关节炎中的临床研究。
