Parren P W
Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Hum Antibodies Hybridomas. 1992 Jul;3(3):137-45.
Production of human monoclonal antibodies (MAbs) of predefined specificity using conventional hybridoma technology has proved to be difficult. Immunotherapeutic intervention in humans with rodent MAbs, however, is disadvantageous because of the antigenicity of these proteins and may result in human antibody responses against this foreign agent. To circumvent this problem, recombinant DNA techniques have been developed to transplant the specificity of a rodent MAb into a human antibody. Two basic approaches are being employed: first, combining rodent MAb variable regions with human constant regions; and more recently, "reshaping" human MAbs by grafting complementarity-determining regions (CDR) into the human antibody framework. These humanized MAbs can now be used to study human Fc-dependent effector mechanisms in detail, which seems essential to optimize potential in vivo application.
事实证明，使用传统杂交瘤技术生产具有预定特异性的人单克隆抗体（MAb）很困难。然而，用啮齿动物单克隆抗体对人类进行免疫治疗干预是不利的，因为这些蛋白质具有抗原性，可能会导致人体针对这种外来物质产生抗体反应。为了解决这个问题，已经开发出重组DNA技术，将啮齿动物单克隆抗体的特异性移植到人类抗体中。目前采用了两种基本方法：第一，将啮齿动物单克隆抗体可变区与人类恒定区结合；最近，通过将互补决定区（CDR）嫁接到人类抗体框架中来“重塑”人单克隆抗体。现在，这些人源化单克隆抗体可用于详细研究人Fc依赖性效应机制，这似乎是优化潜在体内应用的关键。
