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Abatacept



Abatacept (marketed as Orencia) is a fusion protein composed of an immunoglobulin fused to the extracellular domain of CTLA-4, a molecule capable of binding B7. Abatacept is a selective costimulation 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.

Additional recommended knowledge

Contents

Mechanism of action

Ordinarily, full T cell activation requires 1) binding of the T cell receptor to the antigen-MHC complex on the antigen presenting cell (APC) and 2) a costimulatory signal provided by the binding of the T cell's CD28 protein to the B7 protein on the APC. Abatacept, which contains a high-affinity binding site for B7, works by binding to the B7 protein on APCs and preventing them from delivering the costimulatory signal to T cells, thus preventing the full activation of T cells.[1][2]

Abatacept is the basis for the second-generation belatacept currently being tested in clinical trials. In organ transplantation, it is intended to provide extended graft survival while limiting the toxicity generated by standard immune-suppressing regimens such as calcineurin inhibitors (eg, ciclosporin).

Indications

Abatacept is currently approved for use in rheumatoid arthritis patients who have had an inadequate response to one or more DMARDs.[3] It is useful in delaying the progression of structural damage and reducing symptoms of rheumatoid arthritis. However, it should not be used in combination with anakinra or TNF antagonists.[4] It is also likely to be beneficial in the treatment of psoriasis and in organ transplantation.[citation needed]

Abatacept is currently in trial[5] for the treatment of patients suffering moderate to severe active ulcerative colitis, where response to standard treatment has failed to bring about remission.

Structure

Abatacept is a fusion protein composed of the extracellular domain of CTLA-4 with the hinge, CH2, and CH3 domains of IgG1.[4]

Similar agents

References

  1. ^ ABATACEPT & BELATACEPT: the CTLA-4-Igs. Healthvalue.net. Retrieved on 2007-05-25.
  2. ^ Dall'Era M, Davis J (2004). "CTLA4Ig: a novel inhibitor of co-stimulation". Lupus 13 (5): 372–376. PMID 15230295.
  3. ^ Bristol-Myers Squibb (March 13 2007). ORENCIA labelPDF (110 KiB). United States Food and Drug Administration. Retrieved on 2007-05-25.
  4. ^ a b Moreland L, Bate G, Kirkpatrick P (2006). "Abatacept". Nature Reviews Drug Discovery 5: 185–186. PMID 16557658.
  5. ^ A Study of Abatacept in Patients With Active Ulcerative Colitis. ClinicalTrials.gov. United States National Institutes of Health (May 11 2007). Retrieved on 2007-05-25. ClinicalTrials.gov Identifier NCT00410410.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Abatacept". A list of authors is available in Wikipedia.
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