Abdeldaim Dalia T, Schindowski Katharina
Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany.
Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
Pharmaceutics. 2023 Sep 28;15(10):2402. doi: 10.3390/pharmaceutics15102402.
Monoclonal therapeutic antibodies have revolutionized the treatment of cancer and other diseases. Fc engineering aims to enhance the effector functions or half-life of therapeutic antibodies by modifying their Fc regions. Recent advances in the Fc engineering of modern therapeutic antibodies can be considered the next generation of antibody therapy. Various strategies are employed, including altering glycosylation patterns via glycoengineering and introducing mutations to the Fc region, thereby enhancing Fc receptor or complement interactions. Further, Fc engineering strategies enable the generation of bispecific IgG-based heterodimeric antibodies. As Fc engineering techniques continue to evolve, an expanding portfolio of Fc-engineered antibodies is advancing through clinical development, with several already approved for medical use. Despite the plethora of Fc-based mutations that have been analyzed in in vitro and in vivo models, we focus here in this review on the relevant Fc engineering strategies of approved therapeutic antibodies to finetune effector functions, to modify half-life and to stabilize asymmetric bispecific IgGs.
单克隆治疗性抗体彻底改变了癌症和其他疾病的治疗方式。Fc工程旨在通过修饰治疗性抗体的Fc区域来增强其效应功能或半衰期。现代治疗性抗体的Fc工程的最新进展可被视为下一代抗体疗法。人们采用了各种策略，包括通过糖工程改变糖基化模式以及对Fc区域引入突变，从而增强Fc受体或补体相互作用。此外，Fc工程策略能够产生基于双特异性IgG的异二聚体抗体。随着Fc工程技术的不断发展，越来越多的Fc工程抗体正在推进临床开发，其中一些已获批用于医学用途。尽管在体外和体内模型中已经分析了大量基于Fc的突变，但在本综述中，我们将重点关注已获批治疗性抗体的相关Fc工程策略，以微调效应功能、改变半衰期并稳定不对称双特异性IgG。
