Abstract
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.
Authors
Jeffrey S. Boyles, Dorota Sadowski, Scott Potter, Aleksandra Vukojicic, James Parker, William Y. Chang, Yanfei L. Ma, Mark G. Chambers, James Nelson, Barbra Barmettler, Eric M. Smith, Kara Kersjes, Evan R. Himes, Chaohua Lin, Jonathan Lucchesi, Jaladhi Brahmbhatt, Ramtin Sina, Jennifer A. Martin, Evan Maestri, Christopher M. Wiethoff, Gregory L. Dyas, Matthew D. Linnik, Songqing Na, Derrick R. Witcher, Alison Budelsky, Kira Rubtsova
Figure 5
Inhibition of BCR capping and downstream BCR signaling with LY3541860 treatment.
