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.
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
- ^ ABATACEPT & BELATACEPT: the CTLA-4-Igs. Healthvalue.net. Retrieved on 2007-05-25.
- ^ Dall'Era M, Davis J (2004). "CTLA4Ig: a novel inhibitor of co-stimulation". Lupus 13 (5): 372–376. PMID 15230295.
- ^ Bristol-Myers Squibb (March 13 2007). ORENCIA labelPDF (110 KiB). United States Food and Drug Administration. Retrieved on 2007-05-25.
- ^ a b Moreland L, Bate G, Kirkpatrick P (2006). "Abatacept". Nature Reviews Drug Discovery 5: 185–186. PMID 16557658.
- ^ 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.
| Immunomodulators - Immunosuppressants (L04) |
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| Monoclonal antibodies | TNF inhibitors (Infliximab, Adalimumab, Certolizumab pegol), Afelimomab, Aselizumab, Atlizumab, Atorolimumab, Basiliximab, Belimumab, Bertilimumab, Cedelizumab, Clenoliximab, Daclizumab, Dorlimomab aritox, Dorlixizumab, Eculizumab, Efalizumab, Elsilimomab, Erlizumab, Faralimomab, Fontolizumab, Galiximab, Gantenerumab, Gavilimomab, Golimumab, Gomiliximab, Ibalizumab, Inolimomab, Ipilimumab, Keliximab, Lebrilizumab, Lerdelimumab, Lumiliximab, Maslimomab, Mepolizumab, Metelimumab, Morolimumab, Muromonab-CD3, Natalizumab, Nerelimomab, Ocrelizumab, Odulimomab, Omalizumab, Otelixizumab, Pascolizumab, Pexelizumab, Reslizumab, Rovelizumab, Ruplizumab, Siplizumab, Talizumab, Telimomab aritox, Teneliximab, Teplizumab, Tocilizumab, Toralizumab, Vapaliximab, Vepalimomab, Visilizumab, Zanolimumab, Ziralimumab, Zolimomab aritox |
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| -imus | Abetimus, Difirolimus, Dofosirolimus, Everolimus, Gifosirolimus, Gusperimus, Pimecrolimus, Safosirolimus, Sirolimus, Tacrolimus, Temsirolimus, Torolimus, Zotarolimus |
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| -cept (Fusion protein) | Abatacept, Alefacept, Belatacept, TNF inhibitor (Etanercept) |
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| Other | Anakinra, Azathioprine, Ciclosporin, Leflunomide, Methotrexate, Mycophenolic acid, Thalidomide |
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