Dutertre Charles-Antoine, Teillaud Jean-Luc
INSERM UMRS 872, Centre de Recherche des Cordeliers, Université Paris 5 et Université Paris 6, Paris, France;
J Soc Biol. 2006;200(4):377-86. doi: 10.1051/jbio:2006041.
After early difficulties due in part to their mouse origin and questionable selection criteria, monoclonal antibodies have become major therapeutic tools thanks to more and more sophisticated molecular engineering. They are now used in a growing number of therapeutic areas. Molecular engineering has focused on the improvement of antibody affinity, the reduction of immunogenicity due to the murine origin of the first generation of monoclonal antibodies and on the increase of antibody effector properties, initially limited by their murine origin. The current success of antibodies raises new challenges that the scientific and medical communities are taking up: design of antibodies with optimized functional properties, with lower side effects, design of new molecular formats (drug-coupled antibodies, bi-specific antibodies, antibodies with optimized half-lives), detection and selection of "responder" patients. As a new antibody generation is quickly emerging, the future of antibodies is already at sight: development of oligoclonal strategies where cocktails of monoclonal antibodies are used, rationale selection of eligible patients, bulk production at lower costs. To date, twenty-three monoclonal antibodies have received an approval in the United States and/or in Europe and more than two hundred and fifty are currently evaluated in clinical trials. A new wave is coming...
在早期因部分源于小鼠及选择标准存疑而遇到困难后，由于越来越复杂的分子工程技术，单克隆抗体已成为主要的治疗工具。它们如今在越来越多的治疗领域得到应用。分子工程技术主要致力于提高抗体亲和力、降低因第一代单克隆抗体源于小鼠而产生的免疫原性，以及增强抗体效应特性，而抗体效应特性最初因源于小鼠而受到限制。目前抗体取得的成功带来了科学界和医学界正在应对的新挑战：设计具有优化功能特性、副作用更小的抗体，设计新的分子形式（药物偶联抗体、双特异性抗体、半衰期优化的抗体），检测和选择“有反应”的患者。随着新一代抗体迅速涌现，抗体的未来已初见端倪：开发使用单克隆抗体组合的寡克隆策略，合理选择合适的患者，以更低成本进行大规模生产。迄今为止，已有23种单克隆抗体在美国和/或欧洲获得批准，目前有250多种正在临床试验中进行评估。新的浪潮即将到来……
