Novartis Institutes for BioMedical Research, Basel, Switzerland.
Adv Exp Med Biol. 2017;1053:265-294. doi: 10.1007/978-3-319-72077-7_13.
Monocolonal antibodies are valuable potential new tools for meeting unmet needs in treating infectious dieseases and to provide alternatives and supplements to antibiotics in these times of growing resistance. Especially when considering the ability to screen for antibodies reacting to very diverse target antigens and the ability to design and engineer them to work specifically to hit and overcome their strategies, like toxins and their hiding in specific cells to evade the immuneresponse and their special features enabling killing of the infectious agents and or the cells harbouring them. Antibodies are generally very safe and adverse effects of treatments with therapeutic antibodies are usually related to exaggeration of the intended pharmacology. In this chapter general safety considerations for the use of antibodies is reviewed and the general procedures for nonclinical testing to support their clinical development. Special considerations for anti-infective mAb treatments are provided including the special features that makes nonclinical safety programs for anti-infective mAbs much more simple and restricted. However at a cost since only limited information for clinical safety and modeling can be derived from such programs. Then strategies for optimally designing antibodies are discussed including the use of combination of antibodies. Finally ways to facilitate development of more than the currently only three approved mAb based treatments are discussed with a special focus on high costs and high price and how collaboration and new strategies for development in emerging markets can be a driver for this.
单克隆抗体是极具价值的潜在新工具，可满足治疗传染病方面的未满足需求，并为这些日益增长的耐药时代的抗生素提供替代品和补充。尤其是考虑到筛选针对非常多样化的靶抗原的抗体的能力，以及设计和工程抗体专门用于靶向和克服其策略的能力，如毒素及其在特定细胞中的隐藏以逃避免疫反应，以及它们能够杀死感染剂和/或携带它们的细胞的特殊功能。抗体通常非常安全，治疗性抗体治疗的不良反应通常与预期药理学的夸大有关。本章回顾了使用抗体的一般安全性考虑因素，以及支持其临床开发的非临床测试的一般程序。提供了针对抗感染单克隆抗体治疗的特殊考虑因素，包括使抗感染单克隆抗体的非临床安全性计划更加简单和受限的特殊特征。然而，这是有代价的，因为只能从这些计划中获得有限的临床安全性和建模信息。然后讨论了优化设计抗体的策略，包括使用抗体组合。最后，讨论了促进目前仅批准三种基于单克隆抗体的治疗方法之外的更多治疗方法的开发的策略，特别关注高成本和高价格，以及合作和新兴市场的新开发策略如何成为这方面的驱动力。
