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A nondepleting anti-CD19 antibody impairs B cell function and inhibits autoimmune diseases. 2023
Jeffrey S Boyles, and
Dorota Sadowski, and
Scott Potter, and
Aleksandra Vukojicic, and
James Parker, and
William Y Chang, and
Yanfei L Ma, and
Mark G Chambers, and
James Nelson, and
Barbra Barmettler, and
Eric M Smith, and
Kara Kersjes, and
Evan R Himes, and
Chaohua Lin, and
Jonathan Lucchesi, and
Jaladhi Brahmbhatt, and
Ramtin Sina, and
Jennifer A Martin, and
Evan Maestri, and
Christopher M Wiethoff, and
Gregory L Dyas, and
Matthew D Linnik, and
Songqing Na, and
Derrick R Witcher, and
Alison Budelsky, and
Kira Rubtsova
Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
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.
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James Nelson, and
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Chaohua Lin, and
Jonathan Lucchesi, and
Jaladhi Brahmbhatt, and
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