上游技术 | 全面介绍单抗高甘露糖修饰调控中的挑战和对策 - 知乎
治疗性抗体的Fc糖基化修饰类型和比例对临床疗效和安全性具有重要作用。 其中，氮糖基化修饰（N-Glycosylation）中的高甘露糖型（HM）会影响药物的疗效（ADCC）、药代动力学和稳定性。 内源性IgG中HM水平非常低，但市售的治疗性抗体中HM水平明显较高，故需加强调控。 糖基化修饰对工艺变化较敏感，调控HM修饰水平和维持批次/规模间HM一致性具有很大的挑战性。 本文深入剖析了相关的细胞反应过程、分子特征和培养工艺条件对HM的影响，并综述了开发和优 …
单抗药物高甘露糖修饰的调控策略 - 知乎 - 知乎专栏
2021年3月24日 · 糖基化修饰 在维持抗体分子的空间构象、稳定抗体的结构、维持抗体的生物学功能等方面发挥着重要的作用，进而对 药物半衰期 、有效性和安全性产生影响，故糖基化通常是抗体类药物的CQA（Critical Quality Attributes）之一，各国药品监管机构均要求对抗体类药物的糖基化程度进行严格的控制。
The Formidable Challenge of Controlling High Mannose-Type N ... - PubMed
High mannose-type N-glycans (HM) affect efficacy (in terms of antibody-dependent cell cytotoxicity), pharmacokinetics, and stability. While in endogenous IgGs the HM levels are very low, they are significantly higher in marketed therapeutic mAbs.
Structural basis of mammalian high-mannose - Nature
2020年2月14日 · In combination with alanine scanning mutagenesis and hydrolytic activity measurements of EndoBT-3987 point mutants, we present here the comprehensive structural basis of its catalytic and substrate...
High-mannose glycans on the Fc region of therapeutic IgG …
2011年3月18日 · Relative levels of high-mannose 5 (M5) glycan decreased as a function of circulation time, whereas other glycans remained constant. These results demonstrate that therapeutic IgGs containing Fc high-mannose glycans are cleared more rapidly in humans than other glycan forms.
Biological function, regulatory mechanism, and clinical application …
2023年11月1日 · This dual ligand–receptor coupling effect induced by mannose and MTX can selectively target cancer cells expressing corresponding receptors, enabling the delivery of high-dose chemotherapeutic drugs to cancer cells with low nonspecific distribution.
The Formidable Challenge of Controlling High Mannose
2020年10月1日 · High mannose-type N-glycans (HM) affect efficacy (in terms of antibody-dependent cell cytotoxicity), pharmacokinetics, and stability. While in endogenous IgGs the HM levels are very low, they are significantly higher in marketed therapeutic mAbs.
The Formidable Challenge of Controlling High Mannose-Type
2020年6月29日 · High mannose-type N-glycans (HM) affect efficacy (in terms of antibody-dependent cell cytotoxicity), pharmacokinetics, and stability. While in endogenous IgGs the HM levels are very low, they are significantly higher in marketed therapeutic mAbs.
High-Mannose N-Glycans as Malignant Progression Markers in …
2022年3月18日 · High-mannose-type N-glycans were higher in the dysplastic region than in carcinoma, which correlates to increased proliferation of the cells. We observed changes in the cancer invasive front, including higher expression of α2,3-linked sialic acids which followed the glycosylation pattern of the carcinoma region.
Modulation of high mannose levels in N-linked glycosylation …
In this study, we describe efforts to modulate the high-mannose (HM) levels of a biosimilar mAb produced in a Chinese hamster ovary cell fed-batch process. Because the HM level of the mAb was observed to impact ADCC activity, it was desirable to match it to the innovator mAb's levels.