Development of a microfluidic platform for self-governing selection of individual B-cells using bioresponsive hydrogels: a source of fully human therapeutic antibodies

Monoclonal antibodies (mAb) are the biggest class of biopharmaceuticals used against cancer, inflammatory and autoimmune diseases. As the ability of the human immune system to generate highly specific mAb is unmatched by any man-made approach, several technologies have been developed to generate fully human (FH)-mAb. Among those, single B-cell screening has emerged as a powerful technique. In this project, two KU Leuven groups will join their complementary expertise to (1) establish ground-breaking concepts for selection of individual B-cells producing FH-mAb of interest and (2) implement this for a particular identification of ADAMTS13 specific autoantibodies directly from thrombotic thrombocytopenic purpura (TTP) patients. Starting from the in-house established, high-throughput microwell-array platform, which empowers easy isolation and downstream analysis of single cells, we will further advance this technology by incorporating hydrogels in the microwell fabrication. Here, we will develop stimuli-responsive hydrogels for B-cell selection using external stimuli (e.g. light) and a completely innovative bioresponsive hydrogel to enable individual B-cells driving their own selection if presenting a specific antibody. This project will have large cross-disciplinary impact in the fields ranging from developing technologies for single cell analysis/generation of FH-mAb to developing specific human anti-ADAMTS13 antibodies with high therapeutic, prognostic and diagnostic value.