MD-LC-MS for structure-function characterization of therapeutic antibodies (Jelle De Vos, MDCW 2025)

🎤 Presenter: Jelle De Vos (RIC group, Kortrijk, Belgium)

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💡 Book in your calendar: 17th Multidimensional Chromatography Workshop (MDCW) 13 - 15. January 2026

Abstract

The biopharmaceutical industry has undergone a remarkable transformation in recent decades, with monoclonal antibodies (mAbs) becoming one of the most prominent therapeutics for the treatment of life-threatening diseases including cancer and autoimmune diseases. This success has resulted in the development of multiple formats of antibodies, designed to further enhance the therapeutic potential. With sales values exceeding $220 billion in 2023, which is expected to reach $500 billion by 2030, mAbs still rule the charts of most sold pharmaceutical.

Antibody therapeutics not only boast an enormous therapeutic potential, but at the same time also have an immense structural complexity as a result of the biosynthetic process and subsequent manufacturing and storage. These heterogeneous molecular giants exert different functions, facilitated by the Fab or Fc part, including antigen, neonatal fragment crystallizable receptor (FcRn) and Fc-gamma receptor (FcγR) binding. The latter two, are crucial in, respectively, regulating half-life of mAbs in circulation and triggering the immune system through antibody-dependent cellular cytotoxicity. mAb binding to the latter is highly sensitive to amino acid substitutions and post-translational modifications such as glycosylation, oxidation, deamidation and isomerization and it is primordial to understand the impact of these structural attributes on functionality. As such, a thorough analysis of their structure and function is essential.

This talk will highlight the advances made in multidimensional liquid chromatography (MD-LC) in hyphenation to mass spectrometry (MS) to elegantly study structure/function relationships of mAbs in detail. Set-ups with FcRn and FcγRIIIa affinity chromatography implemented will be discussed.