2. Academic Validation
  3. A nondepleting anti-CD19 antibody impairs B cell function and inhibits autoimmune diseases

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

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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