A humanized IL-2 fusion protein enhances T regulatory cells in vivo and restrains disease in a murine model of Alopecia Areata 4760

Abstract Description Alopecia Areata (AA) is a common autoimmune disease that presents as nonscarring hair loss. AA is associated with a collapse of immune privilege of the hair follicle, marked by increased MHC expression, immune cell infiltrates and a pro-inflammatory milieu. NKG2D-expressing CD8 T cells have been identified as primary disease effectors (Teff). Our lab has identified that emergence of disease is marked by a large expansion of Teff that results in them outnumbering Tregs 20-fold. We hypothesized that pharmacologic enhancement of the Treg pool may be an effective strategy for modulating disease. While low dose recombinant human IL-2 (hIL-2) for the purpose of Treg expansion has not shown great promise for AA patients, IL-2 fusion proteins have shown benefits in other disease models and offer advantages over hIL-2. HCW9302 is a recombinant fusion protein containing two human IL-2 domains fused to a soluble human tissue factor domain. It has a longer half-life than hIL-2 and can selectively expand/activate human and murine Tregs. Using a murine skin-graft induction model of AA, we observed HCW9302 treatment protected mice from developing AA. We also noted a significant reduction in the number of Teff found infiltrating the skin and a recovery of skin Tregs to outnumber Teff 4:1. Overall, our findings suggest that Treg enhancement is effective at restraining disease and provides translational insight for the use of IL-2 fusion proteins as a therapeutic strategy for patients with AA. Funding Sources Supported by NIH AR077194 ; VA BX004907; T32AI007485 Topic Categories Therapeutic Approaches to Autoimmunity (THER)