Discovery and Characterization of a Fully Human Monoclonal Antibody Inhibitor of Plasma Kallikrein for the Treatment of Plasma Kallikrein-Mediated Edema

Abstract

Plasma kallikrein (pKal) is a serine protease responsible for generating the vasodilator bradykinin, and is mainly regulated by C1 inhibitor (C1-INH). Patients with hereditary angioedema (HAE) have deficient levels of functional C1-INH, leading to unpredictable attacks of debilitating edema via dysregulated pKal-mediated bradykinin generation. Inhibition of pKal is a viable therapeutic option for HAE, as demonstrated by the efficacy of ecallantide, a specific pKal inhibitor, for treatment of acute HAE attacks.