To view this video content in its entirety, click on the "Access Content" button and login to your account.

If you do not have an account, register for free.

Please note that the account you create here is different than your Keystone Symposia account at www.keystonesymposia.org used to register for our multi-day conferences and is uniquely for viewing our virtual content.


  0      0

On Demand

Anti-CD19, B cell Inhibiting, Non-depleting Antibody: Novel Approach for the Treatment of Autoimmunity


Mar 25, 2022 10:00am ‐ Mar 25, 2022 10:00am


Free

Description

B cells contribute to multiple aspects of autoimmune disorders through autoantibody production, antigen presentation, cytokine secretion, and formation of tertiary lymphoid structures. B cell targeting therapies have been developed and approved for treatment of autoimmune diseases. Many approved B cell targeted therapies deplete B cells through targeting CD20 (rituximab, ocrelizumab, etc). However, CD20-mediated B cell depletion has limitations including incomplete depletion of tissue resident pathogenic B cells, inability to target CD20-negative B cells (plasmablasts), and a long recovery time for B cells. Thus, developing therapies with more efficacy on tissue resident B cells and a non-depleting mechanism of action is highly desirable.
Here we describe a novel, non-depleting, B cell inhibiting, anti-human CD19 antibody LY3541860 which binds human and cynomolgus monkey (cyno) CD19 with high affinity, does not induce ADCC or CDC, and does not cause B cell apoptosis. LY3541860 inhibited B cell activation, proliferation, and differentiation of primary human and cyno B cells ex vivo. LY3541860 also inhibited human B cell activation in vivo in humanized mice. Administration of anti-CD19 antibodies in cyno did not cause reduction of B cells and resulted in complete receptor occupancy.
We also developed a non-depleting anti-mouse CD19 antibody with similar characteristics as the anti-human CD19 antibody. The anti-mouse CD19 antibody was used to compare effects of B cell inhibition with B cell depletion in multiple mouse models of autoimmunity. Our data demonstrate that treatment with the anti-mouse CD19 antibody ameliorated clinical symptoms in multiple mouse autoimmune models including collagen-induced arthritis (CIA), non-obese diabetic (NOD) and experimental autoimmune encephalomyelitis (EAE). Moreover, this anti-mouse CD19 antibody demonstrated improved efficacy in all tested mouse autoimmune models compared with an anti-CD20 depleting antibody. No B cell depletion was noted in any of the in vivo models tested while B cell depletion was evident with the anti-CD20 antibody. Improved efficacy seen with the non-depleting CD19 antibody may be due to targeting CD20-/CD19+ plasmablasts, as well as bypassing limited B cell depletion in tissues.
Taken together, these data suggest that a non-depleting anti-CD19 antibody may demonstrate superior efficacy in treatment of autoimmune conditions compared with B cell depleting therapies.

Speaker(s):

You must be logged in and own this session in order to post comments.