CTLA4Ig

CTLA-4 is expressed on the surface of a subpopulation of activated T lymphocytes and binds with high affinity to molecules of the B7 family that are present on B cells and antigen-presenting cells. CTLA-4Ig is a fusion protein of the extracellular domain of CTLA-4 with the Fc portion of IgG1, which serves as a soluble receptor. Therefore, this molecule prevents CTLA-4/B7 interaction by blocking T-cell activation and T-cell-dependent B-cell functions in vivo. In animal studies, treatment of New Zealand Black/New Zealand White (NZB/NZW) mice resulted in an improved survival rate as well as regression of nephritis (Finck et al. 1994). Moreover, there is evidence that the combination of CTLA-4Ig with an ICOS-Ig fusion protein that blocks the binding of ICOS expressed on activated T cells to its ligand potentiates the beneficial effects of CTLA-4Ig in a murine model of SLE (Ramanujam et al. 2002). Clinical studies with CTLA-4Ig in patients with lupus nephritis are being initiated, and one compound (BMS-188667) currently is being investigated in clinical trials for patients with rheumatoid arthritis and psoriasis.

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