一种新型的 BAFF 特异性抑制剂 AMG623 肽结合物可减少 B 细胞数量，并改善自身免疫性疾病的小鼠模型的预后。
A novel modality of BAFF-specific inhibitor AMG623 peptibody reduces B-cell number and improves outcomes in murine models of autoimmune disease.
机构信息
Department of Inflammation, Amgen Inc., Thousand Oaks, CA 91320, USA.
出版信息
Clin Exp Rheumatol. 2012 Mar-Apr;30(2):197-201. Epub 2012 Apr 13.
OBJECTIVES
AMG623, also known as A-623, is an antagonist of B-cell activating factor (BAFF). The present study was to evaluate the effects of AMG623 on murine models of autoimmune diseases.
METHODS
AMG623 was generated through phage library. Inhibitory activities of AMG623 against human and murine BAFF were measured by biacore binding and BAFF-mediated B-cell proliferation assay. Pharmacological effects of AMG623 were studied in BALB/c mice, collagen-induced arthritis model (CIA) and in the NZBxNZW F1 lupus model.
RESULTS
AMG623 binds to both soluble and cell surface BAFF. AMG623 blocks both human murine BAFF binding to the receptors. Treatment of AMG623 resulted in B-cell number reduction, and improvement of arthritis and lupus development in mice.
CONCLUSIONS
AMG623 is a novel modality of BAFF antagonist. AMG623 is a potential therapeutic agent for the treatment of SLE, rheumatoid arthritis, and other B-cell-mediated autoimmune diseases.
目的
AMG623，也称为 A-623，是 B 细胞激活因子（BAFF）的拮抗剂。本研究旨在评估 AMG623 对自身免疫性疾病小鼠模型的影响。
方法
通过噬菌体文库生成 AMG623。通过生物层干涉结合和 BAFF 介导的 B 细胞增殖测定来测量 AMG623 对人源和鼠源 BAFF 的抑制活性。在 BALB/c 小鼠、胶原诱导关节炎模型（CIA）和 NZBxNZW F1 狼疮模型中研究 AMG623 的药理学作用。
结果
AMG623 结合可溶性和细胞表面 BAFF。AMG623 阻断人源和鼠源 BAFF 与受体的结合。AMG623 治疗导致 B 细胞数量减少，并改善了小鼠的关节炎和狼疮发展。
结论
AMG623 是一种新型的 BAFF 拮抗剂。AMG623 是治疗系统性红斑狼疮、类风湿性关节炎和其他 B 细胞介导的自身免疫性疾病的潜在治疗药物。
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