Generation of Regulatory T cells ex-vivo for the treatment of systemic lupus eryt

DESCRIPTION (provided by applicant): Present pharmaceutical agents used to treat chronic, immune-mediated inflammatory diseases associated with significant morbidity and mortality generally do not lead to remission and have serious toxic side effects. Thisproposal offers a strategy to harness the immune system to treat systemic lupus erythematosus (SLE), a disease of generalized autoimmunity. The product will consist of the patient's own blood T cells stimulated ex-vivo to become therapeutic suppressor cells. In future clinical trials large numbers of this product will be transferred back to the patient as a medicine to ameliorate disease. Proof of concept for phase 1 studies will be to show that na ve CD4+ cells from healthy donors and subjects with SLE stimulated ex-vivo with a proprietary regulatory composition develop potent suppressive activity and protective effects. endogenous regulatory T cells. Principal developmental milestones will be to show that: 1) the product stably expresses Foxp3; 2) the product has significant suppressive activity on autologous T cells both in vitro and in vivo in immunodeficient mice; 3) unlike endogenous regulatory T cells, the product will be resistant to the inhibitory effects of proinflammatory cytokines; and 4) the product generated from SLE T cells suppresses both spontaneous polyclonal IgG and autoantibody production by lupus B cells. If this personalized T cell therapy is safe and successful in future clinical trials and can be produced cost effectively, this approach can become the next paradigm for not only the treatment of autoimmune diseases, but also for prevention of allograft rejection in a manner that will minimize the use of toxic anti-inflammatory or immunosuppressive agents. PUBLIC HEALTH RELEVANCE: Present pharmaceutical agents used to treat life-threatening autoimmune diseases do not generally lead to remission and have many toxic side effects. Our approach is to harness the patient's own immune system to treat systemic lupus erythematosus, one of the most severe autoimmune diseases,. Here the product will be the patient's own immune cells stimulated outside the body using a proprietary methodology to acquire the capacity to halt the progression of the disease In future clinical trials large numbers of this product will be transferred back to the patient to use as a medicine to treat the disease instead of the currently used agents.