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裘霁宛,孔永,陈卫,等. 抗人Ⅰ型干扰素受体亚基1人源化单克隆抗体的制备和鉴定[J]. 中国药科大学学报,2024,55(3):404 − 411. DOI: 10.11665/j.issn.1000-5048.2024031401
引用本文: 裘霁宛,孔永,陈卫,等. 抗人Ⅰ型干扰素受体亚基1人源化单克隆抗体的制备和鉴定[J]. 中国药科大学学报,2024,55(3):404 − 411. DOI: 10.11665/j.issn.1000-5048.2024031401
QIU Jiwan, KONG Yong, CHEN Wei, et al. Generation and characterization of humanized monoclonal antibody against human IFNAR1[J]. J China Pharm Univ, 2024, 55(3): 404 − 411. DOI: 10.11665/j.issn.1000-5048.2024031401
Citation: QIU Jiwan, KONG Yong, CHEN Wei, et al. Generation and characterization of humanized monoclonal antibody against human IFNAR1[J]. J China Pharm Univ, 2024, 55(3): 404 − 411. DOI: 10.11665/j.issn.1000-5048.2024031401

抗人Ⅰ型干扰素受体亚基1人源化单克隆抗体的制备和鉴定

Generation and characterization of humanized monoclonal antibody against human IFNAR1

  • 摘要: Ⅰ型干扰素在系统性红斑狼疮(SLE)等自身免疫性疾病的发病机制中发挥重要作用,采用抗体阻断其信号转导通路具有潜在的治疗作用。本研究以人Ⅰ型干扰素受体亚基1(IFNAR1)重组蛋白为抗原免疫新西兰白兔,采用B细胞克隆技术筛选兔抗人IFNAR1单克隆抗体,经过人源化改造获得QX006N。体外研究结果显示,QX006N能特异性地结合人IFNAR1,亲和力约108 pmol/L,可阻断Ⅰ型干扰素信号通路及其介导的生物学效应。本研究为开发靶向干预Ⅰ型干扰素信号途径用于治疗SLE的抗体药物提供了坚实的基础。

     

    Abstract: Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Monoclonal antibody shows therapeutic potential by blocking the signaling pathway. This study used recombinant human subunit 1 of the type I interferon receptor (IFNAR1) protein to immunize New Zealand white rabbits, and applied B cell cloning technology to screen and obtain rabbit parental antibodies. After humanization modification, QX006N was obtained. In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L, and neutralize the type I interferon signaling pathway and this pathway mediated biological effects. This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.

     

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