Impact of Glycosylation on Effector Functions of Therapeutic IgG.
Impact of Glycosylation on Effector Functions of Therapeutic IgG.
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DOI：
10.3390/ph3010146
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发表时间：
2010-01-12
期刊：
影响因子：
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通讯作者：
Teillaud JL
中科院分区：
文献类型：
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作者：
Abès R;Teillaud JL
人免疫球蛋白在Fc区的Cγ2区只有一个保守的糖基化位点，这解释了每个免疫球蛋白中存在两个糖基。这些Ig G糖核在许多Ig G效应器功能中起着关键作用。本文就Ig G Fc糖基化的主要特征及血清Ig G糖基化异常作一综述。我们还讨论了糖基化对单抗和IVIg效应器功能的影响，以及如何设计这些分子。几种治疗性抗体现在已经被设计成无或低岩藻糖抗体，目前正在进行临床试验。与高度岩藻糖化的同类相比，它们表现出与激活FcγRIIIA的结合增加，并引发强烈的抗体依赖细胞毒作用。它们代表了新一代治疗性抗体，可能在患者中显示出更好的临床疗效，特别是在需要细胞毒抗体的癌症患者中。
Human IgG has only one conserved glycosylation site located in the Cγ2 domain of the Fc region that accounts for the presence of two sugar moieties per IgG. These IgG sugar cores play a critical role in a number of IgG effector functions. In the present review, we describe the main characteristics of IgG Fc glycosylation and some abnormalities of serum IgG glycosylation. We also discuss how glycosylation impacts on monoclonal antibodies (mAbs) and IVIg effector functions and how these molecules can be engineered. Several therapeutic antibodies have now been engineered to be no- or low-fucose antibodies and are currently tested in clinical trials. They exhibit an increased binding to activating FcγRIIIA and trigger a strong antibody-dependent cell cytotoxicity (ADCC) as compared to their highly-fucosylated counterparts. They represent a new generation of therapeutic antibodies that are likely to show a better clinical efficacy in patients, notably in cancer patients where cytotoxic antibodies are needed.