Beck Alain, Debaene François, Diemer Hélène, Wagner-Rousset Elsa, Colas Olivier, Van Dorsselaer Alain, Cianférani Sarah
Centre d'Immunologie Pierre Fabre (CIPF), 5 Av. Napoléon III, BP 60497, 74164, Saint-Julien-en-Genevois, France.
J Mass Spectrom. 2015 Feb;50(2):285-97. doi: 10.1002/jms.3554.
The approval process for antibody biosimilars relies primarily on comprehensive analytical data to establish comparability and high similarity with the originator. Mass spectrometry (MS) in combination with liquid chromatography (LC) and electrophoretic methods are the corner stone for comparability and biosimilarity evaluation. In this special feature we report head-to-head comparison of trastuzumab and cetuximab with corresponding biosimilar and biobetter candidates based on cutting-edge mass spectrometry techniques such as native MS and ion-mobility MS at different levels (top, middle and bottom). In addition, we discuss the advantages and the limitations of sample preparation and enzymatic digestion, middle-up and -down strategies and the use of hydrogen/deuterium exchange followed by MS (HDX-MS). Last but not least, emerging separation methods combined to MS such as capillary zone electrophoresis-tandem MS (CESI-MS/MS), electron transfer dissociation (ETD), top down-sequencing (TDS) and high-resolution MS (HR-MS) that complete the panel of state-of-the-art MS-based options for comparability and biosimilarity evaluation are presented.
抗体生物类似药的审批过程主要依赖全面的分析数据来确立与原研药的可比性和高度相似性。质谱（MS）与液相色谱（LC）及电泳方法相结合是可比性和生物相似性评估的基石。在本专题中，我们报告了基于前沿质谱技术（如不同水平（顶部、中部和底部）的天然质谱和离子淌度质谱），对曲妥珠单抗和西妥昔单抗与其相应生物类似药及优化生物药候选药物进行的直接比较。此外，我们还讨论了样品制备和酶解、中上和中下策略以及氢/氘交换后质谱分析（HDX-MS）的优缺点。最后但同样重要的是，还介绍了与质谱联用的新兴分离方法，如毛细管区带电泳-串联质谱（CESI-MS/MS）、电子转移解离（ETD）、自上而下测序（TDS）和高分辨率质谱（HR-MS），这些方法完善了用于可比性和生物相似性评估的一系列基于质谱的先进方法。
