Combined antibody therapy for type 1 diabetes (107.2)

Abstract

Abstract Studies have shown that oral tolerance is effective in treating different models of autoimmune diseases including type 1 diabetes (T1D). Both T and B cells play important roles in the development of T1D. Antibodies targeting either T or B cells have shown to be effective in treating T1D in both patients and NOD mice. However, individual antibodies are only effective in a proportion of those treated. Furthermore, the beneficial effects have not been long lasting. To test whether the combination of anti-CD20 and oral anti-CD3 treatment can improve the efficacy in prevention and reversal of T1D and prolong the beneficial effects, we treated a group of human CD20 transgenic NOD mice with anti-hCD20 monoclonal antibody and oral anti-CD3. The results suggested that anti-CD20 and anti-CD3 have synergistic effects in the diabetes prevention and reversal. Mechanistic studies have demonstrated that the combination treatment induced FoxP3+ Tregs and enhanced the regulatory function of Treg. A subset of IL-10+ CD4 T cells was also induced in peyer’s patches of the mice treated with combined therapy. Our preliminary study may provide a novel therapeutic approach to treating T1D.