Exploiting protease activation for therapy
Chloe Bleuez, Wolfgang F. Koch, Carole Urbach, Florian Hollfelder, Lutz Jermutus
Abstract
Proteases have crucial roles in homeostasis and disease; and protease inhibitors and recombinant proteases in enzyme replacement therapy have become key therapeutic applications of protease biology across several indications. This review briefly summarises therapeutic approaches based on protease activation and focuses on how recent insights into the spatial and temporal control of the proteolytic activation of growth factors and interleukins are leading to unique strategies for the discovery of new medicines. In particular, two emerging areas are covered: the first is based on antibody therapies that target the process of proteolytic activation of the pro-form of proteins rather than their mature form; the second covers a potentially new class of biopharmaceuticals using engineered, proteolytically activable and initially inactive pro-forms of antibodies or effector proteins to increase specificity and improve the therapeutic window.