人用重组单克隆抗体电荷异质性的研究进展

Progress in research on charge heterogeneity of recombinant monoclonal antibodies for human use

人用重组单克隆抗体是一种具有复杂的翻译后修饰的生物大分子,其微观不均一性导致单克隆抗体药物并不是单一纯净的物质,而是多种产品相关物质的混合物,因此,对这些产品相关的变体及其降解方式的进一步研究尤为重要。几乎所有变体均能导致抗体表面电荷分布的差异,电荷变量因此成为监测抗体降解最灵敏的方式,也是对产品质量一致性分析的一项重要参考标准。本文对几种主要电荷变体的成因、检测方法及其对产品有效性影响的研究进展作一综述。

Therapeutic monoclonal antibodies （mAbs） are biological macromolecules with complex post-translational modifications. Because of their heterogeneity, mAbs are not a pure but a mixture of a variety of product-related substances. A comprehensive understanding of these product-related substances and degradation processes occurring in mAbs is particularly important. As almost all of the variants can cause charge-related heterogeneity, charge variable has become both the most sensitive approach to monitor the degradation of mAb and a reference standard for product quality and consistency. In this paper, the progress in research on causes and detection methods of several major charge variants and the impact on the safety and efficacy of product are reviewed.