Van Bockstaele Femke, Holz Josefin-Beate, Revets Hilde
Ablynx NV, Technologiepark 4, B-9052 Zwijnaarde, Belgium.
Curr Opin Investig Drugs. 2009 Nov;10(11):1212-24.
Evolution has been continuously honing the design of antibodies to function as specific molecular markers that are able to alert the immune system to the presence of pathogenic antigens, and to recruit complement- and Fc receptor-bearing effector cells. During the past 25 years, the versatility of antibodies has been applied to several therapeutic applications. The development of new technologies, combined with data obtained using a new generation of antibody reagents, have allowed the adaptation of the design of antibodies to better match drug development requirements. Nanobodies are therapeutic proteins derived from the heavy-chain variable (VHH) domains that occur naturally in heavy-chain-only Ig molecules in camelidae. These VHH domains are the smallest known antigen-binding antibody fragments. Nanobodies can be easily produced in prokaryotic or eukaryotic host organisms, and their unique biophysical and pharmacological characteristics render these molecules ideal candidates for drug development. This review describes the structural properties of nanobodies and focuses on their unique features, which distinguishes these molecules from other antibody formats and small-molecule drugs. Possible therapeutic applications of nanobodies are discussed and data from phase I clinical trials of the novel 'first-in-class' anti-thrombotic agent ALX-0081 (Ablynx NV) are presented.
进化一直在不断优化抗体的设计，使其作为特定的分子标记物，能够提醒免疫系统病原体抗原的存在，并招募携带补体和Fc受体的效应细胞。在过去25年中，抗体的多功能性已应用于多种治疗应用。新技术的发展，结合使用新一代抗体试剂获得的数据，使得抗体设计得以调整，以更好地满足药物开发需求。纳米抗体是源自重链可变（VHH）结构域的治疗性蛋白质，这些结构域天然存在于骆驼科动物仅含重链的免疫球蛋白分子中。这些VHH结构域是已知最小的抗原结合抗体片段。纳米抗体可以很容易地在原核或真核宿主生物体中产生，其独特的生物物理和药理特性使这些分子成为药物开发的理想候选物。本综述描述了纳米抗体的结构特性，并重点关注其独特特征，这些特征将这些分子与其他抗体形式和小分子药物区分开来。讨论了纳米抗体可能的治疗应用，并展示了新型“同类首创”抗血栓药物ALX-0081（Ablynx NV）一期临床试验的数据。
