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

  • JCI Insight. 2023 Jul 10;8(13):e166137. doi: 10.1172/jci.insight.166137.
Jeffrey S Boyles  1 ,  Dorota Sadowski  2 ,  Scott Potter  2 ,  Aleksandra Vukojicic  2 ,  James Parker  2 ,  William Y Chang  2 ,  Yanfei L Ma  3 ,  Mark G Chambers  3 ,  James Nelson  4 ,  Barbra Barmettler  4 ,  Eric M Smith  4 ,  Kara Kersjes  2 ,  Evan R Himes  3 ,  Chaohua Lin  3 ,  Jonathan Lucchesi  3 ,  Jaladhi Brahmbhatt  1 ,  Ramtin Sina  1 ,  Jennifer A Martin  1 ,  Evan Maestri  2 ,  Christopher M Wiethoff  1 ,  Gregory L Dyas  1 ,  Matthew D Linnik  2 ,  Songqing Na  2 ,  Derrick R Witcher  1 ,  Alison Budelsky  2 ,  Kira Rubtsova  2
Affiliations
  • 1. Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
  • 2. Immunology Discovery, Lilly Biotechnology Center, Lilly Research Laboratories, Eli Lilly and Company, San Diego, California, USA.
  • 3. Immunology Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
  • 4. Biotechnology Discovery Research, Lilly Biotechnology Center, Lilly Research Laboratories, Eli Lilly and Company, San Diego, California, USA.
PMID: 37427592 DOI: 10.1172/jci.insight.166137
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.

Keywords
Adaptive immunity; Autoimmunity; Immunoglobulins; Immunology.
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