A nondepleting anti-CD19 antibody impairs B cell function and inhibits autoimmune diseases.

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
• Journal: JCI insight (JCI Insight) Vol. 8 Issue 13 (07 10 2023) ISSN: 2379-3708 [Electronic] United States
• PMID: 37427592 (Publication Type: Journal Article)

Chemical References

• Antigens, CD19

Topics

• Mice
• Animals
• B-Lymphocytes
• Antigens, CD19
• Autoimmune Diseases (drug therapy)