: A major long-term goal of the OncoImmune LLC is to develop therapeutic agents for the treatment of multiple sclerosis. Compelling evidence indicates that autoreactive T cells are involved in pathogenesis of Multiple Sclerosis (MS). Since the MS patients have accumulated large numbers of autoreactive T cells, a major challenge is to prevent the effector function of pre-existing autoreactive T cells by targeting the molecules involved in the effector function of T cells regardless of their antigen-specificity. In this regard, we have recently established that the CD24 gene is a critical checkpoint, beyond induction of self-reactive T cells, in the development of acute experimental autoimmune encephalomyelitis (A-EAE), a murine model of human MS. More importantly, the fusion protein consisting of the extracellular domain of the CD24 and the Fc portion of the human immunoglobulin (Ig), drastically reduces the clinical symptoms of acute EAE when administrated after self-reactive T cells are produced. In this phase I application, we wish to extend our observation into the relapsing EAE (R-EAE) model that closely resembles the clinical course of human MS. We will produce a large amount of CD24Ig fusion protein or soluble CD24 and test their efficacy in treating relapsing EAE in SJL mice. In addition, the ability of CD24Ig or soluble CD24 to prevent """"""""epitope-spreading"""""""" in antigen recognized by T cells will also be evaluated. Our study will provide solid evidence for the therapeutic potential of CD24-based drugs.