核心岩藻糖基化控制在治疗性抗体研究中的应用

对于人类许多疾病,抗体已成为了一种很重要的治疗制剂。如何进一步提高抗体的效能,是目前研究的主要热点之一。在抗体治疗过程中,抗体依赖性细胞介导的细胞毒作用(antibody dependent cellular cytotoxicity,ADCC)被认为是治疗性抗体临床疗效中一个重要的治疗功能。抗体恒定区Fc片段(crystalline fragment)的糖基化对ADCC起着至关重要的作用,尤其是抗体恒定区的核心岩藻糖基化。近些年来,很多研究报告表明,去除或降低岩藻糖基化的治疗性抗体不论在体内还是在体外都表现出更高的效能。这主要是由于去除或降低岩藻糖基化的治疗性抗体相对于岩藻糖基化的抗体,可以在更低浓度下通过与FcγRIIIa的高亲和力而表现出较强的ADCC作用。因此,去除或降低岩藻糖基化抗体的应用有望成为提高下一代治疗性抗体效能的有效手段。在此综述中,我们主要讨论了控制治疗性抗体恒定区岩藻糖基化的重要性及当前去除或降低岩藻糖基化治疗性抗体的生产控制方法。

Application of core fucosylated control in therapeutic antibodies

Antibodies have become major therapeutic agents in the treatment of many human diseases.How to improve the efficacy of antibodies further is one of the research focuses at present.In the treatment of antibodies,antibody dependent cellular cytotoxicity（ADCC） is considered to be an important therapeutic function for clinical efficacy of therapeutic antibodies.Glycosylation of the antibody constant region Fc fragment is essential for ADCC,especially the core fucosylation.Over the years,there have been a number of reports showing that non-fucosylated or low-fucosylated therapeutic antibodies show more potent efficacy both in vitro and in vivo,mainly because they exhibit strong ADCC at lower concentrations with much higher efficacy compared to fucosylated counterparts through its high binding to Fc γ receptor IIIa（FcγRIIIa）.Thus,the application of non-fucosylated or low-fucosylated antibodies is expected to be a powerful approach to the design of the next generation therapeutic antibodies with improved efficacy.In this review,we mainly discuss the importance of controlling the fucosylation attached to the Fc region of therapeutic antibodies and the current technologies for production of non-fucosylated or low-fucosylated therapeutic antibodies.