Tihamer Orban
Section on Immunology and Immunogenetics, Joslin Diabetes Center, One Joslin Place, Boston, MA. 02215, USA

Abstract:

Type 1 diabetes mellitus (T1DM) is the most common chronic childhood disease, a serious burden to the patients, to their families and to the society. The underlying autoimmune process is the result of the imbalance between the self-antigen specific autoagressive and regulatory T cells.

We report the results of a double blind, placebo controlled phase I clinical trial (sponsored by the Immune Tolerance Network) of a novel drug in patients with recently diagnosed T1DM. This new antigen based therapeutic approach uses human insulin B-chain in an incomplete Freund adjuvant (IFA) as a single intramuscular injection. We enrolled 12 patients (6 in each arm), who received either active or the placebo vaccinations within 3 months of their diagnoses and were followed for 2 years. Safety monitoring revealed excellent safety profile in both arms. Mixed meal stimulated C-peptide responses were tested every 6 months and we found no statistical differences, however there was a better trend in the stimulated C-peptide decline in the insulin B-chain vaccinated group after three months of the vaccination. All patients vaccinated with the autoantigen and none who received placebo developed robust insulin specific humoral and T cells responses. In the autoantigen vaccinated patients, but not in the placebo recipients, insulin B-chain specific CD4+ T cells could be isolated and cloned from the peripheral blood and showed phenotypic and functional characteristics of regulatory T cells. 

Human insulin B-chain based novel drug therapy showed excellent safety profile in patients recently diagnosed with T1DM and induced a robust immune response generating autoantigen specific regulatory T cells.