Discussion
TYPE 1 DIABETES, AUTOIMMUNE DISEASES
Combination therapies of immune modulation and antigen are appealing in organ-specific autoimmune diseases like type 1 diabetes. We demonstrated the safety and biological activity of an 8 week treatment of oral AG019 (The rationale for the development of AG019 and for this clinical investigation was that hIL-10 locally delivered at the intestinal mucosa could induce IL-10-producing CD4The complementary mode of action of teplizumab to the AG019-induced antigen-specific tolerogenic milieu can occur on multiple levels. Anti-CD3 increases Tr1s locally in the GI tract [In addition to the biological activity of AG019 monotherapy, this is the first study examining combination therapy with teplizumab in humans. Combination therapies, either simultaneously or sequentially combining immune modulation with beta cell protective interventions, have been proposed as strategies to help sustain the stabilising effect of teplizumab on functional beta cell mass [This study has a few limitations that restrict conclusions. First, sample sizes are small in all of the groups, and we did not have a teplizumab-only group to compare the findings with for antigen-specific T cells or metabolic effects. For immune measures, while assay technical variation has been validated for islet antigen-specific CD8In summary, AG019 provides a new technology for oral delivery of antigen-specific immune modulators that is safe and induces biological activity. The beneficial safety profile and the convenient route of administration open paths for prolonged AG019 treatment in future studies, which will further address the potential beneficial therapeutic effects for the treatment of type 1 diabetes.