a Molecular & Analytical Development , Bristol-Myers Squibb , New Jersey , USA.
MAbs. 2018 Feb/Mar;10(2):222-243. doi: 10.1080/19420862.2017.1412025. Epub 2018 Jan 5.
Antibody-drug conjugates (ADCs) are a growing class of biotherapeutics in which a potent small molecule is linked to an antibody. ADCs are highly complex and structurally heterogeneous, typically containing numerous product-related species. One of the most impactful steps in ADC development is the identification of critical quality attributes to determine product characteristics that may affect safety and efficacy. However, due to the additional complexity of ADCs relative to the parent antibodies, establishing a solid understanding of the major quality attributes and determining their criticality are a major undertaking in ADC development. Here, we review the development challenges, especially for reliable detection of quality attributes, citing literature and new data from our laboratories, highlight recent improvements in major analytical techniques for ADC characterization and control, and discuss newer techniques, such as two-dimensional liquid chromatography, that have potential to be included in analytical control strategies.
抗体药物偶联物（ADCs）是一类日益增长的生物治疗药物，其中将有效小分子与抗体连接。ADC 非常复杂且结构多样，通常含有多种与产品相关的物质。在 ADC 开发中最具影响力的步骤之一是确定关键质量属性，以确定可能影响安全性和疗效的产品特性。然而，由于 ADC 相对于母体抗体具有更高的复杂性，因此需要深入了解主要质量属性，并确定其关键性，这是 ADC 开发中的一项重大任务。在这里，我们通过引用我们实验室的文献和新数据，综述了开发过程中的挑战，特别是对质量属性进行可靠检测方面的挑战，重点介绍了 ADC 特性和控制方面主要分析技术的最新改进，并讨论了二维液相色谱等新技术，这些技术可能会被纳入分析控制策略中。
