Agonist antibody discovery: Experimental, computational, and rational engineering approaches

Agonist antibodies that activate cellular signaling have emerged as promising therapeutics for treating myriad pathologies. Unfortunately, the discovery of rare antibodies with the desired agonist functions is a major bottleneck during drug development. Nevertheless, there has been important recent progress in discovering and optimizing agonist antibodies against a variety of therapeutic targets that are activated by diverse signaling mechanisms. Herein, we review emerging high-throughput experimental and computational methods for agonist antibody discovery as well as rational molecular engineering methods for optimizing their agonist activity.