Unmet Need
Global incidence of autoimmune disease is on the rise, and currently one in twelve Americans (including one in 9 women) suffer from autoimmune disease. Particularly, Type 1 Diabetes (T1D) represents a highly prevalent autoimmune disease, affecting over 20 million people. These diseases occur when the body’s immune system incorrectly attacks healthy cells and tissues. To combat autoimmune diseases, recent treatment strategies have focused on regulatory T cells (Tregs) which modulate immune responses. Immunocytokines (IC) consisting of an antibody and IL-2 cytokine have recently developed as a method of preferentially engaging and expanding such Tregs. However, antigen specificity, which is an important therapeutic characteristic for improving targeted efficacy has yet to be engineered in conjunction with existing ICs.
Technology Overview
Tolerogenic antigen presenting cells (TolAPCs) consisting of a biodegradable particle surface-conjugated with a combination of IC and autoantigen-loaded MHC tetramers have been developed. TolAPCs are synthesized by forming a polymer core and covalently attaching ICs and specific autoantigen complexes to the surface. To evaluate performance, TolAPCs were incubated in-vitro with CD4+ T cells and compared to free IL-2 cytokine and free IC complexes. TolAPCs selectively stimulated Treg populations and achieved the same stimulation as free IC and greater stimulation than free IL-2. In an in-vivo mouse model, TolAPCs also increased the ratio of Treg cells compared to a no treatment condition. Altogether, the inventors have demonstrated efficacy of TolAPCs as an antigen specific IC based regulatory T cell modulator.
Stage of Development
A proof of concept was demonstrated in-vitro and in an in-vivo mouse model.
