Monoclonal antibodies (mAbs) are currently the largest and fastest growing class of biopharmaceuticals, and they address unmet medical needs, e.g., in oncology and in auto-immune diseases. Their clinical efficacy and safety is significantly affected by the structure and composition of their glycosylation profile which is commonly heterogeneous, heavily dependent on the manufacturing process, and thus susceptible to variations in the cell culture conditions. Glycosylation is therefore considered a critical quality attribute for mAbs. Commonly, in currently marketed therapeutic mAbs, the glycosylation profile is suboptimal in terms of biological properties such as antibody-dependent cell-mediated cytotoxicity or may give rise to safety concerns due to the presence of non-human glycans. This article will review recent innovative developments in chemo-enzymatic glycoengineering, which allow generating mAbs carrying single, well-defined, uniform Fc glycoforms, which confers the desired biological properties for the target application. This approach offers significant benefits such as enhanced Fc effector functions, improved safety profiles, higher batch-to-batch consistency, decreased risks related to immunogenicity and manufacturing process changes, and the possibility to manufacture mAbs, in an economical manner, in non-mammalian expression systems. Overall, this approach could facilitate and reduce mAb manufacturing costs which in turn would translate into tangible benefits for both patients and manufacturers. The first glycoengineered mAbs are about to enter clinical trials and it is expected that, once glycoengineering reagents are available at affordable costs, and in-line with regulatory requirements, that targeted remodeling of antibody Fc glycosylation will become an integral part in manufacturing the next-generation of immunotherapeutics.

中文翻译：

---

糖工程抗体：面向下一代免疫疗法

单克隆抗体（mAbs）是目前最大和增长最快的生物药物类别，它们满足了未满足的医学需求，例如在肿瘤学和自身免疫性疾病中。它们的临床疗效和安全性受到其糖基化分布图的结构和组成的影响，糖基化分布图通常是异质的，在很大程度上取决于制造过程，因此容易受到细胞培养条件变化的影响。因此，糖基化被认为是单克隆抗体的关键质量属性。通常，在当前市售的治疗性mAb中，就生物学特性而言，如抗体依赖性细胞介导的细胞毒性，糖基化谱是次优的，或者由于存在非人聚糖而可能引起安全性问题。本文将回顾化学酶糖工程技术的最新创新进展，这些进展将允许产生携带单一，定义明确，均一的Fc糖型的mAb，从而赋予目标应用所需的生物学特性。这种方法具有显着的优势，例如增强的Fc效应子功能，改进的安全性，更高的批次间一致性，降低了与免疫原性和生产工艺变化有关的风险，以及以经济的方式在非哺乳动物中生产mAb的可能性。表达系统。总体而言，这种方法可以促进和降低mAb的制造成本，进而为患者和制造商带来切实的利益。首批糖工程化单克隆抗体即将进入临床试验，预计，