Siberil S, Dutertre C-A, Boix C, Teillaud J-L
Unité Inserm 255, université Paris-VI-Pierre-et-Marie-Curie, centre de recherches biomédicales des Cordeliers, France.
Transfus Clin Biol. 2005 Jun;12(2):114-22. doi: 10.1016/j.tracli.2005.04.016.
Thirty years after their discovery by Milstein and Köhler, monoclonal antibodies have now come of age as therapeutics. Nineteen monoclonal antibodies are on the market and/or have got authorization to be used for the treatment of severe diseases. Many technical efforts have been devoted over the last two decades to the generation of second generation mAbs with better affinities, decreased immunogenicity and optimized effector functions. The development of molecular engineering techniques applied to antibody molecules has also made it possible to design bi-specific antibodies and fusion molecules exhibiting different modules with bi-functional activities. The use of proteomics and genomics combined with phage display allows now the rapid selection of antibodies directed against new targets at a high rate. Many efforts are currently focused on the selection of high-responder patients, the optimization of antibody delivery, schemes of infusion, antibody pharmaco-kinetics and bio-distribution, as well as on a better control of the severe side-effects generated by some antibody treatments.
在米尔斯坦和科勒发现单克隆抗体30年后，单克隆抗体如今已发展成为成熟的治疗药物。19种单克隆抗体已上市和/或已获授权用于治疗严重疾病。在过去二十年里，人们付出了许多技术努力来研发具有更高亲和力、更低免疫原性和优化效应功能的第二代单克隆抗体。应用于抗体分子的分子工程技术的发展，也使得设计具有双功能活性的不同模块的双特异性抗体和融合分子成为可能。蛋白质组学和基因组学与噬菌体展示相结合的应用，现在能够快速、高效地筛选针对新靶点的抗体。目前，许多努力都集中在筛选高反应性患者、优化抗体递送、输注方案、抗体药代动力学和生物分布，以及更好地控制某些抗体治疗产生的严重副作用上。
