Abès Riad, Dutertre Charles-Antoine, Teillaud Jean-Luc
Laboratoire français du fractionnement et des biotechnologies, Les Ulis, France. Inserm U872, Paris, F-75006 France.
Med Sci (Paris). 2009 Dec;25(12):1011-9. doi: 10.1051/medsci/200925121011.
The therapeutic use of monoclonal antibodies is growing exponentially. Our knowledge on antibody structure, in particular that of IgG1, largely used in the clinic, has progressed remarkably. However, some formidable challenges still remain to be confronted, among which the increase of a yet-limited antibody efficacy, the lowering of the frequency of serious clinical adverse events, and the establishment of pre-clinical models that can be reliably extrapolated to humans represent major goals. The selection of relevant target antigens with regard to the pathology to be treated and to the expected effects of the antibody used is also a critical parameter. Facing these challenges, the amazing molecular plasticity of antibodies, as well as new antibody engineering approaches based on the most recent insights on the structure and biology of antibodies and their targets represent areas of research that will make monoclonal antibodies remarkable drugs for human health in a near future.
单克隆抗体的治疗用途正在呈指数级增长。我们对抗体结构的认识,尤其是临床上广泛使用的IgG1的结构,已经取得了显著进展。然而,仍有一些巨大挑战有待应对,其中提高目前仍有限的抗体疗效、降低严重临床不良事件的发生频率,以及建立能够可靠地外推至人类的临床前模型是主要目标。针对待治疗的病理状况以及所用抗体的预期效果选择相关靶抗原也是一个关键参数。面对这些挑战,抗体惊人的分子可塑性,以及基于对抗体及其靶标的结构和生物学的最新认识而产生的新抗体工程方法,代表了未来不久将使单克隆抗体成为有益于人类健康的卓越药物的研究领域。