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Abstract

Click to add/remove this article to your list of 'My Favorites' Anti-CD20 Antibody Synergizes with Proinsulin Plasmid To Prevent the Onset of T1D in NOD Mice

Year: 2011

Abstract Number: 1009-P

Authors: GHANASHYAM SARIKONDA, SOWBARNIKA SACHITHANANTHAM, HIDEKI GARREN, ANDREW CHAN, MATTHIAS VON HERRATH

Institutions: La Jolla, CA, San Mateo, CA, San Francisco, CA

Results: B-cells play a role in T1D, likely as antigen presenting cells rather than through antibody-production. Results from a clinical trial in T1D using a B-cell depleting anti-CD20 antibody, published in NEJM recently show that anti-CD20 treatment was efficient at preserving C-peptide production over a time span of 6 months, in some T1D patients. In NOD mice, therapeutic administration of proinsulin plasmid was efficient at reverting the recent onset T1D disease. In order to understand the mechanism and increase the efficacy of anti-CD20 mAb mediated protection, we used a newly developed anti-mouse-CD20 antibody in combination with proinsulin-expressing plasmid to generate antigen specific tolerance and prevent T1D. We found that administration of anti-CD20 by itself delayed the onset of hyperglycemia in NOD mice. While >90% of untreated NOD mice became diabetic by 30 weeks of age, only 60% of mice that received 50 μg of anti-CD20 were diabetic. In the peripheral blood, B-cells were significantly reduced on day 7 after anti-CD20 administration and remained low until day 21. There was a compensatory increase in both CD4 and CD8 T-cell numbers; however, the frequencies of Tregs were not increased. To improve the efficacy of anti-CD20 mediated protection, we combined the administration of anti-CD20 with a plasmid expressing proinsulin. Among those mice that received anti-CD20 and the proinsulin-expressing plasmid, 75% of the mice remained diabetes free at 30 wks of age. Thus, while the administration of anti-CD20 alone delays the onset of hyperglycemia in NOD mice, combining the administration of anti-CD20 with the proinsulin plasmid offers greater protection in reducing the incidence of diabetes.