IL2-based Immunotherapy for Lupus

Systemic lupus erythematosus SLE is a prototypic autoimmune disease that affects at least million Americans Current immunosuppressive treatments are effective but can be accompanied by infections and toxicity especially when applied over a longer period of time Hence there remains a significant unmet need for safe and more effective treatments It is well established that patients with SLE are marked by reduced regulatory T cells and acquired deficiency of interleukin IL Transient treatment with low dose recombinant IL increases regulatory T cell number while blocking T follicular helper cells Hence the treatment reduced autoantibody formation and immune complex deposition without inducing systemic immune suppression These data strongly support development of IL based therapy Importantly low dose rIL therapy safely achieved significant efficacy in a small clinical trial However current low dose rIL therapy has a very short half life and causes local reaction at injection sites with an unwanted increase in several innate immune cell types such as natural killer cells and eosinophils To obtain ideal outcomes in patients we have designed a long acting IL analog APT that promises to generate low and stable circulating levels of IL related agonist The innovative drug candidate will enable selective stimulation of regulatory T cells while minimizing negative clinical effects Importantly a better efficacy and safety profile has been demonstrated in multiple animal models The specific aim of this Phase I SBIR proposal is to determine whether twice weekly treatment with mAPT for weeks will more effectively halt the disease progression for days of follow up compared with low dose rmIL recombinant murine IL in the mouse model of SLE at the time of disease onset The innovative approach involves the treatment with a novel IL analog APT to restore regulatory T cell function in systemic lupus erythematosus SLE that will arrest the autoimmune process and thereby halt disease progression