Roguska Michael, Kaymakcalan Zehra, Salfeld Jochen
Abbott Bioresearch Center, Worcester, Massachusetts, USA.
Curr Protoc Pharmacol. 2005 Jan 1;Chapter 9:Unit 9.7. doi: 10.1002/0471141755.ph0907s27.
The number of therapeutic antibodies approved by regulatory agencies as novel drugs and the number of antibodies in development has increased significantly. The modular nature of antibody structure has enabled researchers to more predictably design therapeutic antibodies by choosing appropriate functional features most appropriate for a given antibody target and clinical indication. Advances in recombinant antibody technologies have allowed the routine generation of antibodies that can satisfy stringent drug design criteria, such as low immunogenicity, high affinity, target specificity, and commercially viable manufacturing methods. Engineering design opportunities exist for both the variable and the constant regions that encompass, in addition to antigen specificity and affinity, effector functions that mediate immune complex clearance or pharmacokinetics. These are discussed in the context of relevant in vivo and in vitro technologies, such as human IgG transgenic mice, phage display, and biologics manufacturing. Finally, therapeutic antibodies are compared with traditional drugs with respect to target class, selectivity, route of administration, intellectual property issues, and lead discovery and optimization.
监管机构批准作为新药的治疗性抗体数量以及处于研发阶段的抗体数量显著增加。抗体结构的模块化性质使研究人员能够通过选择最适合特定抗体靶点和临床适应症的适当功能特征，更可预测地设计治疗性抗体。重组抗体技术的进步使得能够常规生产满足严格药物设计标准的抗体，如低免疫原性、高亲和力、靶标特异性和商业上可行的生产方法。除了抗原特异性和亲和力外，包含介导免疫复合物清除或药代动力学的效应器功能的可变区和恒定区都存在工程设计机会。这些将在相关的体内和体外技术背景下进行讨论，如人IgG转基因小鼠、噬菌体展示和生物制品生产。最后，将治疗性抗体与传统药物在靶点类别、选择性、给药途径、知识产权问题以及先导化合物发现和优化方面进行比较。
