Sanz Laura, Cuesta Angel M, Compte Marta, Alvarez-Vallina Luis
Servicio de Inmunologia, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Acta Pharmacol Sin. 2005 Jun;26(6):641-8. doi: 10.1111/j.1745-7254.2005.00135.x.
Antibody-based therapeutics are beginning to realize the promise enclosed in their early denomination as magic bullets. Initial disappointment has turned into clinical and commercial success, and engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials. Recent structural and functional data have allowed the design of a new generation of therapeutic antibodies, with strategies ranging from complement-mediated and antibody-dependant cellular cytotoxicity enhancement to improved cytotoxic payloads using toxins, drugs, radionucleids and viral delivery. This review considers the structure of different types of recombinant antibodies, their mechanism of action and how their efficacy has been increased using a broad array of approaches. We will also focus on the additional benefits offered by the use of gene therapy methods for the in vivo production of therapeutic antibodies.
基于抗体的治疗药物正开始实现其早期被称为“神奇子弹”时所蕴含的前景。最初的失望已转变为临床和商业上的成功，目前工程抗体在临床试验中的生物制药中占比超过30%。最近的结构和功能数据使得新一代治疗性抗体的设计成为可能，其策略包括补体介导和抗体依赖性细胞毒性增强，以及使用毒素、药物、放射性核素和病毒递送等改进的细胞毒性载荷。本文综述了不同类型重组抗体的结构、作用机制，以及如何通过一系列广泛的方法提高其疗效。我们还将重点关注使用基因治疗方法在体内生产治疗性抗体所带来的额外益处。
