Probing antibody-target interactions in living systems

Antibodies have become an attractive class of therapeutic agents for multiple types of diseases, mainly owing to their high target selectivity and target affinity. The target binding properties are critical for antibodies’ efficacy and toxicity. However, we still heavily rely on the static in vitro system to characterize antibody’s target binding properties, and their behaviors in vivo – the actual sites of actions – remain undefined. Our group has developed a bioluminescence resonance energy transfer (BRET) imaging approach that directly supports the measurement of the binding dynamics between antibodies and their targets in the native tissue environment. Built upon the imaging data, we have developed a spatially resolved computational model analyzing the longitudinal BRET imaging data to explore the kinetics of antibody-target binding. Our work has yielded insights into the physiological factors affecting antibody-target interactions in their sites of action, which are critical for improving antibody-based therapeutics.