Half-life extended IL-10 for the treatment of murine autoimmune diabetes 9408

Abstract Description IL-10 is a canonically immunosuppressive cytokine that has shown efficacy in preclinical models of type 1 diabetes, but the need for frequent administration of the cytokine over long durations prevented clinical advancement. The recent approval of the anti-CD3 antibody teplizumab (Tzield™) suggests immunomodulation is an effective strategy in preventing the onset of T1D. Here, we aim to show that the use of a half-life extended, serum albumin-fused IL-10 reduces the necessary duration of IL-10 treatment in the NOD model to something resembling the treatment schedule of teplizumab. NOD mice received a two-week course of either wild-type IL-10 or the half-life extended SA-IL-10 at 4 weeks (early in the disease process) or 10 weeks (after diabetogenic T cells have developed). We observed that the SA-IL-10 delays disease onset relative to mice that receive only the wild-type cytokine and hypothesize this has to do with the cytokine’s action on the myeloid compartment, reducing antigen presentation to and co-stimulation of autoreactive T cells. This is further supported by flow cytometric data in studies using SA-IL-10 in the experimental autoimmune encephalomyelitis model of autoreactive neurological disease. We believe that SA-IL-10 could prove beneficial in that it acts on a separate immune process than that hypothesized by teplizumab, creating the opportunity for a synergistic and more timing-agnostic combination therapy to suppress multiple steps of disease pathogenesis. Funding Sources Chicago Immunoengineering Innovation Center (CIIC) Topic Categories Therapeutic Approaches to Autoimmunity (THER)