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单克隆抗体(monoclonal antibody,McAb)在疾病的预防、诊断及治疗方面显示出重要的作用。1975年,K?觟hler和Milstein[1]共同创立了杂交瘤技术,首次获得了人工制备的McAb,然而,由该方法制备的McAb存在以下缺陷: ①由于其为鼠源性,被人免疫系统识别后可产生人抗鼠抗体(human anti-mouse antibody,HAMA); ②鼠源性McAb不能有效激活人补体和Fc受体相关的效应系统,且在体内的半衰期较短[2]。为了克服上述缺陷,利用基因工程技术对鼠源性McAb进行了不同程度的人源化,产生了各种人源化抗体。
McAb的人源化研究主要经历了3个发展阶段:将鼠源性McAb的可变区和人抗体的恒定区组装合成人-鼠嵌合抗体(human-mouse chimeric antibody); 仅保留鼠源性McAb可变区中与抗原结合的互补决定区(complementarity-determining region,CDR),制备CDR移植抗体(grafted antibody)或改型抗体(reshaped antibody); 利用抗体库及转基因技术制备全人源抗体(fully human antibody)[3]。
单克隆抗体人源化技术研究进展
Advances on humanized monoclonal antibody technology
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摘要: 随着分子生物学技术的发展,应用DNA重组技术、抗体库技术及转基因技术对鼠源性单抗进行人源化改造,先后出现了嵌合抗体、互补决定区移植抗体和全人源抗体,它们从不同角度克服了鼠源性单抗临床应用的不足,为单克隆抗体在临床诊断及治疗中的应用带来了新的曙光,该文对单克隆抗体人源化技术的研究进展作一综述。Abstract: With the development of molecular biology, people can humanize mouse monoclonal antibody with DNA recombination, antibody library and transgenic technology which developed antibody techniques from chimeric and grafted antibody to fully human antibody.The humanized monoclonal antibodies overcome the clinical shortage of mouse monoclonal antibody from different angles, also bring a new dawn to the diagnosis and treatment of human disease.This article will summarize the progress on the humanization of mouse monoclonal antibody.
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