Repurposing ubiquitination for innovative antibody conjugation

Abstract

Conjugated antibodies are critical tools across research, diagnostics, and therapeutic applications. These conjugates range from fluorescently labelled antibodies used in imaging, to bispecific antibodies for dual antigen targeting, and antibody-drug conjugates (ADCs) for the targeted delivery of cytotoxic agents. However, current antibody conjugation strategies face several key challenges, notably the efficiency of the conjugation process and the heterogeneity of the resulting conjugates. These factors can significantly influence the stability, pharmacokinetics, toxicity profiles, and batch-to-batch consistency of the conjugated products. Together with the growing interest in multispecific antibodies and antibody complexes for dual or higher-order targeting, this presses for advances in conjugation techniques.

This thesis aims to develop and optimize covalent, site-specific conjugation technologies to enhance the efficiency, reproducibility, and functional performance of antibody conjugates. Additionally, it explores the application of synthetic peptide chemistry to overcome current limitations, offering better control over conjugation sites, improved reproducibility, and enhanced functional performance. By addressing these challenges, the work sets out to contribute to the development of next-generation antibody-based tools with broad implications for diagnostics, research, and therapeutic interventions.