Monoclonal antibodies directed against human FcRn and their applications
Monoclonal antibodies directed against human FcRn and their applications
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DOI：
10.4161/mabs.4.2.19397
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发表时间：
2012-03-01
期刊：
影响因子：
5.3
通讯作者：
Roopenian, Derry C.
中科院分区：
文献类型：
--
作者：
Christianson, Gregory J.;Sun, Victor Z.;Roopenian, Derry C.
MHC I类样Fc受体（FcRn）是一种细胞内运输Fc受体，其独特地负责IgG亚类抗体的延长血清半衰期及其跨细胞屏障运输的能力。通过执行这些功能，FcRn影响抗体生物学和病理生物学的许多方面。其在控制IgG药代动力学中的关键作用已被用于治疗性抗体和相关生物制剂的设计。FcRn还运输血清白蛋白，并且负责白蛋白缀合的治疗剂的增强的药代动力学性质。由于缺乏可靠的抗人FcRn的血清学试剂，对FcRn及其治疗应用的理解受到限制。在这里，我们描述了一个新的面板的高度特异性单克隆抗体（mAb）针对不同的表位特异性的人FcRn的属性。我们表明，该抗体面板可用于研究人FcRn的组织表达模式，选择性地阻断IgG和血清白蛋白结合人FcRn在体外和抑制FcRn功能在体内。该mAb组为探索人FcRn的生物学和评价治疗性FcRn阻断策略提供了强大的资源。
The MHC class I-like Fc receptor (FcRn) is an intracellular trafficking Fc receptor that is uniquely responsible for the extended serum half-life of antibodies of the IgG subclass and their ability to transport across cellular barriers. By performing these functions, FcRn affects numerous facets of antibody biology and pathobiology. Its critical role in controlling IgG pharmacokinetics has been leveraged for the design of therapeutic antibodies and related biologics. FcRn also traffics serum albumin and is responsible for the enhanced pharmacokinetic properties of albumin-conjugated therapeutics. The understanding of FcRn and its therapeutic applications has been limited by a paucity of reliable serological reagents against human FcRn. Here, we describe the properties of a new panel of highly specific monoclonal antibodies (mAbs) directed against human FcRn with diverse epitope specificities. We show that this antibody panel can be used to study the tissue expression pattern of human FcRn, to selectively block IgG and serum albumin binding to human FcRn in vitro and to inhibit FcRn function in vivo. This mAb panel provides a powerful resource for probing the biology of human FcRn and for the evaluation of therapeutic FcRn blockade strategies.