Human FcRn Transgenic Mice for Pharmacokinetic Evaluation of Therapeutic Antibodies
Human FcRn Transgenic Mice for Pharmacokinetic Evaluation of Therapeutic Antibodies
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DOI：
10.1007/978-1-60761-058-8_6
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Sproule, Thomas J.
中科院分区：
文献类型：
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作者：
Roopenian, Derry C.;Christianson, Gregory J.;Sproule, Thomas J.
治疗性单克隆抗体被广泛认为是治疗越来越多的人类疾病（包括癌症和自身免疫性疾病）最有前途的手段。在很大程度上，单克隆抗体治疗的功效是因为IgG抗体在体内的持久性大大延长。然而，传统的啮齿动物模型并不反映人类抗体的药代动力学。负责延长抗体持久性的关键分子是主要组织相容性复合物 I 类 Fc 受体 FcRn。我们描述了人类 FcRn 转基因小鼠模型以及如何有效地利用它们对治疗性抗体进行临床前药代动力学评估。
Therapeutic monoclonal antibodies arc widely recognized to be a most promising means to treat an increasing number of human diseases, including cancers and autoimmunity. To a large extent, the efficacy of monoclonal antibody treatment is because IgG antibodies have greatly extended persistence in vivo. However, conventional rodent models do not mirror human antibody pharmacokinetics. The key molecule responsible for the extended persistence antibodies is the major histocompatibility complex class I family Fc receptor, FcRn. We describe human FcRn transgenic mouse models and how they can be exploited productively for the preclinical pharmacokinetic evaluation of therapeutic antibodies.