Tregitope-mediated antigen-specific tolerance induction in autoimmune and allergic disease in vivo. (THER5P.831)

Abstract

Abstract Tregitopes are a novel class of therapeutic compounds that harness the activity of regulatory T cells (Tregs) and represent a promising new approach for the treatment of autoimmune and inflammatory diseases. Tregitopes are Treg epitopes found in IgG that provide beneficial immunomodulatory effects, paralleling those attributed to intravenous immunoglobulin (IVIG), in vitro and in vivo. When APCs present Tregitopes to Tregs, APC expression of MHC II, CD80, and CD86 are decreased; expression of the tolerance-associated marker ILT3 is increased. These results are consistent with reported effects of IVIG (Bayry et al. Blood, 2003, 101:758) and the IgG-derived peptide hCDR1 (Sela et al. Immunology, 2009, 128:395). Tregitopes also cause CD4+CD25+FoxP3+ Treg to expand and produce IL-10 in vitro. Evaluation of Tregitope effects in mouse models of MS (EAE), OVA-induced allergic airway disease, and AAV-mediated gene transfer show that effector T cells are modified in the presence of Tregitopes. In OVA-induced allergic airway disease, we observed significant and reproducible expansion of Tregs in conjunction with decreased airway reactivity comparable to, if not greater than, IVIG. We have additional unpublished evidence demonstrating the antigen specificity of tolerance induction using Tregitopes in conjunction with target antigens. Formulated with or without the target antigen, Tregitopes represent a promising new treatment for human immune-mediated disease.