Inhibition of immune costimulation has significant immunosuppressive effects, manifested in the reduction of specific Ab production, prolonging the survival of organ transplants, and inhibiting autoimmune diseases. This rational is the basis for the increasing interest in developing modulators of costimulation for therapeutic uses.
CGEN-15001 is a novel protein which has shown potential for the treatment of autoimmune disorders. CGEN-15001 is a fusion protein consisting of the extracellular region of a previously unknown membrane protein in the B7/CD28 family, CGEN-15001T, fused to an Fc domain. The existence and potential utility of the newly discovered parent protein from which CGEN-15001 is derived, was predicted in silico utilizing Compugen’s Protein Family Members Discovery Platform. CGEN-15001 inhibits T cell activation and Th1 and Th17 differentiation, and promotes Th2 differentiation. In an animal model of multiple sclerosis, short term treatment with CGEN-15001 at onset of remission results in long-term inhibition of disease, dramatic amelioration of disease symptoms and abolishment of relapses. This was accompanied with inhibition of infiltration of reactive T lymphocytes into the central nervous system. The significant beneficial effect of CGEN-15001 in the disease is due to induction of immune tolerance, demonstrated by the inhibition of epitope spreading, the underlying phenomenon which causes the relapsing nature of the disease. CGEN-15001 was also demonstrated to have a therapeutic effect in an animal model of rheumatoid arthritis. In this animal model, CGEN-15001 showed efficacy similar to that observed through TNF-alpha blockade with TNFR-Fc, ENBREL®, a widely used biologic disease modifying anti-rheumatic drug (DMARD). Taken together, the results obtained for CGEN-15001 indicate its therapeutic potential for treatment of multiple autoimmune diseases and inflammatory conditions, such as multiple sclerosis and rheumatoid arthritis.