Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstrasse 6, 52074 Aachen, Germany.
Mol Biotechnol. 2013 Jul;54(3):1056-68. doi: 10.1007/s12033-012-9612-x.
Antibodies and antibody-based drugs are currently the fastest-growing class of therapeutics. Over the last three decades, more than 30 therapeutic monoclonal antibodies and derivatives thereof have been approved for and successfully applied in diverse indication areas including cancer, organ transplants, autoimmune/inflammatory disorders, and cardiovascular disease. The isotype of choice for antibody therapeutics is human IgG, whose Fc region contains a ubiquitous asparagine residue (N297) that acts as an acceptor site for N-linked glycans. The nature of these glycans can decisively influence the therapeutic performance of a recombinant antibody, and their absence or modification can lead to the loss of Fc effector functions, greater immunogenicity, and unfavorable pharmacokinetic profiles. However, recent studies have shown that aglycosylated antibodies can be genetically engineered to display novel or enhanced effector functions and that favorable pharmacokinetic properties can be preserved. Furthermore, the ability to produce aglycosylated antibodies in lower eukaryotes and bacteria offers the potential to broaden and simplify the production platforms and avoid the problem of antibody heterogeneity, which occurs when mammalian cells are used for production. In this review, we discuss the importance of Fc glycosylation focusing on the use of aglycosylated and glyco-engineered antibodies as therapeutic proteins.
抗体和基于抗体的药物是目前增长最快的治疗药物类别。在过去的三十年中，已经批准了 30 多种治疗性单克隆抗体及其衍生物，并成功应用于包括癌症、器官移植、自身免疫/炎症性疾病和心血管疾病在内的多个适应症领域。抗体治疗药物的首选同型是人类 IgG，其 Fc 区域含有一个普遍存在的天冬酰胺残基（N297），作为 N-连接聚糖的接受位点。这些糖链的性质可以决定性地影响重组抗体的治疗性能，其缺失或修饰会导致 Fc 效应功能丧失、更高的免疫原性和不利的药代动力学特征。然而，最近的研究表明，糖基化缺失的抗体可以通过基因工程来展示新的或增强的效应功能，并且可以保留有利的药代动力学特性。此外，在低等真核生物和细菌中生产糖基化缺失的抗体的能力为拓宽和简化生产平台提供了潜力，并避免了在使用哺乳动物细胞进行生产时发生的抗体异质性问题。在这篇综述中，我们讨论了 Fc 糖基化的重要性，重点介绍了糖基化缺失和糖基工程抗体作为治疗性蛋白质的应用。
