Desgranges C
Unité Inserm 03-34, institut de génétique moléculaire, hôpital Saint-Louis, 27, rue Juliette-Dodu, 75010 Paris, France.
Pathol Biol (Paris). 2004 Jul;52(6):351-64. doi: 10.1016/j.patbio.2003.09.017.
More than 25 years after their discovery, monoclonal antibodies are now the most rapid expanding pharmaceutical viable drugs in clinical trials. The emergence of these antibodies was made possible by the development of genetic recombinant techniques. It is now possible to obtain engineered antibodies: chimearic or humanized or fully human monoclonal antibodies via the use of phage display technology or of transgenic mice. These antibodies are tolerable to the human immune system and eleven have been approved for therapeutic by the US Food and Drug Administration (FDA), the majority of them in the past four years. At least an additional 400 monoclonal antibodies are in clinical trials to treat cancer, transplant rejection or to combat autoimmune or infectious diseases. Important advances have been made in the design of highly specific fragment antibodies, fused or not with drugs or radioisotopes, and in the large industrial scale production with different expression systems (bacteria, yeasts, mammalian cells and transgenic plants and animals). In the next future new molecular promising strategies will enhance affinity, stability and expression levels and reduce the price of these engineering monoclonal to permit their use to treat a large number of diseases.
在单克隆抗体被发现25年多后,它们如今是临床试验中增长最为迅速的药用可行药物。基因重组技术的发展使得这些抗体的出现成为可能。现在通过使用噬菌体展示技术或转基因小鼠,可以获得工程抗体:嵌合抗体、人源化抗体或完全人源单克隆抗体。这些抗体可被人体免疫系统耐受,已有11种获得了美国食品药品监督管理局(FDA)的治疗批准,其中大部分是在过去四年获批的。至少还有400种单克隆抗体正在进行临床试验,用于治疗癌症、移植排斥反应或对抗自身免疫性疾病或传染病。在设计高度特异性的片段抗体(无论是否与药物或放射性同位素融合)以及利用不同表达系统(细菌、酵母、哺乳动物细胞以及转基因植物和动物)进行大规模工业生产方面都取得了重要进展。在不久的将来,新的有前景的分子策略将提高亲和力、稳定性和表达水平,并降低这些工程单克隆抗体的价格,从而使其能够用于治疗大量疾病。