Article
作者: Smith, Eric M ; Dyas, Gregory L ; Na, Songqing ; Boyles, Jeffrey S ; Himes, Evan R ; Linnik, Matthew D ; Ma, Yanfei L ; Chambers, Mark G ; Rubtsova, Kira ; Chang, William Y ; Parker, James ; Lin, Chaohua ; Sina, Ramtin ; Potter, Scott ; Martin, Jennifer A ; Barmettler, Barbra ; Kersjes, Kara ; Sadowski, Dorota ; Vukojicic, Aleksandra ; Witcher, Derrick R ; Budelsky, Alison ; Maestri, Evan ; Nelson, James ; Lucchesi, Jonathan ; Wiethoff, Christopher M ; Brahmbhatt, Jaladhi
B cells contribute to multiple aspects of autoimmune disorders, and B cell-targeting therapies, including B cell depletion, have been proven to be efficacious in treatment of multiple autoimmune diseases. However, the development of novel therapies targeting B cells with higher efficacy and a nondepleting mechanism of action is highly desirable. Here we describe a nondepleting, high-affinity anti-human CD19 antibody LY3541860 that exhibits potent B cell inhibitory activities. LY3541860 inhibits B cell activation, proliferation, and differentiation of primary human B cells with high potency. LY3541860 also inhibits human B cell activities in vivo in humanized mice. Similarly, our potent anti-mCD19 antibody also demonstrates improved efficacy over CD20 B cell depletion therapy in multiple B cell-dependent autoimmune disease models. Our data indicate that anti-CD19 antibody is a highly potent B cell inhibitor that may have potential to demonstrate improved efficacy over currently available B cell-targeting therapies in treatment of autoimmune conditions without causing B cell depletion.