Boosting mass spectrometry-based analytics for biopharma

Gstöttner, C.J. (2021)

Doctoral Thesis

Antibody-based drugs are the largest class of biopharmaceuticals produced. They are currently employed to treat diverse diseases such as cancer, cardiovascular or neuronalogical diseases. Whereas some years ago, efforts were focused on developing classical monoclonal antibodies (mAbs), nowadays there is a trend towards engineered antibodies with enhanced functions, such as bispecific antibodies (BsAbs). These molecules increase on structural complexity and bring new challenges for their analytical characterization. Furthermore, the continuous development of new antibody treatments and molecules also increases the pressure in the analytical labs longing for more automation and high-throughput mass spectrometric analysis. This thesis addresses these aspects and provide solutions for improved and efficient characterization of novel antibody therapeutics focusing on mass spectrometric approaches. These approaches are based on multidimensional liquid chromatography or capillary electrophoresis hyphenated to mass spectrometry or on the application of in-source decay fragmentation. Next to structural characterization, in this thesis MS-based approaches have been developed for their functional characterization permitting to study the relationships between antibody structure and function.

• Biopharmaceuticals
• Antibodies
• Mass Spectrometry
• Hyphenation
• Capillary Electrophoresis
• Chromatography
• Binding Assays
• Proteoforms
• SARS-CoV-2 RBD
• Recombinant Proteins

• All authors: Gstöttner, C.J.
• Supervisor: Wuhrer, M.
• Co-supervisor: Domínguez Vega, E.
• Committee: Toes, R.E.M.; Bischoff, R.P.H.; Kohler, I.; Gargano, A.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center [LUMC], Leiden University
• Date: 2021-11-30
• ISBN (print): 9789464193336
• Sponsorship: Horizon 2020 project “Analytics for Biologics” (Grant agreement ID 765502)