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Etanercept : ウィキペディア英語版
Etanercept

Etanercept (trade name Enbrel) is a biopharmaceutical that treats autoimmune diseases by interfering with tumor necrosis factor (TNF; a soluble inflammatory cytokine) by acting as a TNF inhibitor. It has U.S. F.D.A. approval to treat rheumatoid arthritis, juvenile rheumatoid arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. TNF-alpha is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.〔(【引用サイトリンク】title=TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases - Nature Medicine )
Etanercept is a fusion protein produced by recombinant DNA. It fuses the TNF receptor to the constant end of the IgG1 antibody. First, the developers isolated the DNA sequence that codes the human gene for soluble TNF receptor 2, which is a receptor that binds to tumor necrosis factor-alpha. Second, they isolated the DNA sequence that codes the human gene for the Fc end of immunoglobulin G1 (IgG1). Third, they linked the DNA for TNF receptor 2 to the DNA for IgG1 Fc. Finally, they expressed the linked DNA to produce a protein that links the protein for TNF receptor 2 to the protein for IgG1 Fc.
The prototypic fusion protein was first synthesized and shown to be highly active and unusually stable as a modality for blockade of TNF in vivo in the early 1990s by Bruce A. Beutler, an academic researcher then at the University of Texas Southwestern Medical Center at Dallas, and his colleagues.〔Peppel,K. et al. A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J.Exp.Med. 174(6):1483-9, 1991〕〔Peppel,K. et al. Expression of a TNF inhibitor in transgenic mice. J.Immunol. 151(10):5699-703, 1993〕〔Kolls,J. et al. Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer. Proc.Natl.Acad.Sci.USA 91(1):215-9, 1994〕 These investigators also patented the protein,〔U.S. Patent number: 5,447,851〕 selling all rights to its use to Immunex, a biotechnology company that was acquired by Amgen in 2002.
It is a large molecule, with a molecular weight of 150 kDa., that binds to TNFα and decreases its role in disorders involving excess inflammation in humans and other animals, including autoimmune diseases such as ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and, potentially, in a variety of other disorders mediated by excess TNFα.
==Medical uses==
In the USA the FDA has licensed Enbrel for :
*Moderate to Severe Rheumatoid Arthritis (RA) (Nov 1998)
*Moderate to Severe Polyarticular Juvenile Rheumatoid Arthritis (May 1999)
*Psoriatic Arthritis (Jan 2002)
*Ankylosing Spondylitis (AS) (July 2003)
*Moderate to Severe Plaque Psoriasis (April 2004)

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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