重塑一种治疗性CD4抗体。
Reshaping a therapeutic CD4 antibody.
作者信息
Gorman S D, Clark M R, Routledge E G, Cobbold S P, Waldmann H
机构信息
Department of Pathology, University of Cambridge, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1991 May 15;88(10):4181-5. doi: 10.1073/pnas.88.10.4181.
Abstract
An immunosuppressive rat antibody (Campath-9) against human CD4 has been reshaped for use in the management of autoimmunity and the prevention of graft rejection. Two different forms of the reshaped antibody were produced that derive their heavy chain variable region framework sequences from the human myeloma proteins KOL or NEW. When compared to a chimeric form of the CD4 antibody, the avidity of the KOL-based reshaped antibody was only slightly reduced, whereas that of the NEW-based reshaped antibody was very poor. The successful reshaping to the KOL-based framework was by a procedure involving the grafting of human framework sequences onto the cloned rodent variable region by in vitro mutagenesis.
摘要
一种针对人类CD4的免疫抑制大鼠抗体（Campath-9）已被重塑，用于自身免疫性疾病的治疗和移植排斥反应的预防。制备了两种不同形式的重塑抗体，它们的重链可变区框架序列来源于人类骨髓瘤蛋白KOL或NEW。与CD4抗体的嵌合形式相比，基于KOL的重塑抗体的亲和力仅略有降低，而基于NEW的重塑抗体的亲和力则非常差。基于KOL框架的成功重塑是通过一种程序实现的，该程序涉及通过体外诱变将人类框架序列嫁接到克隆的啮齿动物可变区上。
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