Abatacept

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About Abatacept

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Abatacept (marketed as Orencia) is a fusion protein composed of the Fc region of the immunoglobulin IgG1 fused to the extracellular domain of CTLA-4. It is a molecule capable of binding with more avidity to CD80 (B7-1) than to CD86 (B7-2). Abatacept is a selective co-stimulation modulator as it inhibits the costimulation of T cells. It was developed by Bristol-Myers Squibb and is licensed in the United States for the treatment of rheumatoid arthritis in the case of inadequate response to anti-TNFα therapy. Abatacept prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal to T cells to fully activate them. Note that binding of the activation signal without its complementary co-stimulatory signal also helps to enable downregulation of T cells by way of T cell anergy. Simple signaling without co-stimulation allows the cell to recognize the primary signal as "self" and not ramp-up responses for future responses as well. Ordinarily, full T cell activation requires 1) binding of the T cell receptor to the antigen-MHC complex on the APC and 2) a co-stimulatory signal provided by the binding of CD28, a T cell protein, to the B7 protein on the APC. Abatacept,

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