MabMine: Breaking the barrier in conventional antibody discovery

Monoclonal antibodies (mAbs), proteins brought to expression by B-cells, target a specific epitope which makes them interesting as a drug. With more than 100 FDA and EMA-approved drugs, therapeutic mAbs have revolutionized modern medicine. Initially, therapeutic mAbs were generated through hybridoma technology, an inefficient technique that has largely been replaced by screening of phage display libraries and cloning of B-cell receptors (BCR; BCR=mAbs) of single B-cells. The latter enables the discovery of naturally occurring mAbs within the B-cell repertoire induced by infection, vaccination or auto-immunity. Contrary to phage-display, cloning of BCR allows the identification of by nature paired heavy and light antibody chains. It is an efficient, robust, and high-speed technique to identify in vivo matured therapeutic mAbs with correct affinity, stability, and functional properties. This research project focusses on the optimization of this innovative approach by, among other aspects, (1) comprehensively mapping the B-cell immune repertoire after immunization of (humanized) mice, (2) develop assays that allow analyzation of mAbs functional properties during the first screening phase of single B-cells, and (3) create high throughput methods for cloning and sequencing the genes encoding the paired light and heavy mAbs chains. These technological research ambitions will be optimized by applying them to relevant cases in order to, simultaneously, develop novel therapeutic mAbs, for example, for the treatment of viral infections.