Cogné Michel, Duchez Sophie, Pascal Virginie
Université de Limoges, Laboratoire d'immunologie, Faculté de médecine, F-87025 Limoges, France.
Med Sci (Paris). 2009 Dec;25(12):1149-54. doi: 10.1051/medsci/200925121149.
The properties of monoclonal antibodies explain why they are such a successful class of therapeutic molecules. However, pionneered initial antibodies were of murine origin and triggered an immune response which limited the therapeutic potential of the antibody and generated deleterious effects. Consequently, tremendous efforts have been developped to engineer these murine Ig by introducing human sequences in vitro, or in vivo by humanization of murine antibodies, leading to chimeric immunoglobulins, and more recently generation of fully human antibodies in transgenic mice with a more or less diversified V repertoire. These approaches have led to the development of an increasing number of these chimeric or humanized monoclonal antibodies entering pharmaceutical pipelines.
单克隆抗体的特性解释了它们为何是如此成功的一类治疗性分子。然而,最初研发的抗体源自小鼠,会引发免疫反应,这限制了抗体的治疗潜力并产生有害影响。因此,人们付出了巨大努力,通过在体外引入人类序列,或通过对小鼠抗体进行人源化在体内改造这些小鼠免疫球蛋白,从而产生嵌合免疫球蛋白,最近还在具有或多或少多样化V基因库的转基因小鼠中生成了完全人源抗体。这些方法已促使越来越多的此类嵌合或人源化单克隆抗体进入药物研发流程。