Monoclonal antibodies directed against human FcRn and their applications

被引:33
作者
Christianson, Gregory J. [1 ]
Sun, Victor Z. [1 ]
Akilesh, Shreeram [1 ]
Pesavento, Emanuele [1 ]
Proetzel, Gabriele [1 ]
Roopenian, Derry C. [1 ]
机构
[1] Jackson Lab, Bar Harbor, ME 04609 USA
基金
美国国家卫生研究院;
关键词
FcRn; IgG; monoclonal antibody; albumin; therapy; MEDIATED AUTOIMMUNE-DISEASE; PH-DEPENDENT BINDING; THERAPEUTIC ANTIBODIES; CRYSTAL-STRUCTURE; DENDRITIC CELLS; RECEPTOR; IGG; ALBUMIN; COMPLEX; MICE;
D O I
10.4161/mabs.4.2.19397
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:208 / 216
页数:9
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