Tremelimumab

Tremelimumab

drugbox-mab


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Tremelimumab (anti-CTLA4 human monoclonal antibody CP-675,206) (formerly ticilimumab) is a fully human monoclonal antibody produced by Pfizer. It binds to the CTLA-4 molecule, which is expressed on the surface of activated T lymphocytes. Tremelimumab binds to CTLA4 and blocks the binding of the antigen-presenting cell ligands B7-1 and B7-2 to CTLA4, resulting in inhibition of B7-CTLA4-mediated downregulation of T-cell activation; subsequently, B7-1 or B7-2 may interact with another T-cell surface receptor protein, CD28, resulting in a B7-CD28-mediated T-cell activation unopposed by B7-CTLA4-mediated inhibition.Tremelimumab is thought to stimulate patients’ immune systems to attack their tumors. Tremelimumab has been shown to induce durable tumor responses in patients with metastatic melanoma in Phase 1 and Phase 2 clinical studies. See Reuben JM et al., Biologic and immunomodulatory events after CTLA-4 blockade with tremelimumab in patients with advanced malignant melanoma. Cancer. 2006 Jun 1;106 (11):2437-44.

As of June 2007 there are two fully human anti CTLA-4 [http://www.healthvalue.net/ctlaigenglish.html] monoclonal antibodies in advanced clinical trials. Tremelimumab (from Pfizer) is an IgG2, and Ipilimumab (from Medarex and Bristol-Myers Squibb). On April 2, 2008, Pfizer announced that it has discontinued a Phase III clinical trial (A3671009), tremelimumab in patients with advanced melanoma, after the review of interim data showed that the trial would not demonstrate superiority to standard chemotherapy. [ [http://www.businesswire.com/portal/site/pfizer/?ndmViewId=news_view&newsId=20080401006838&newsLang=en Pfizer Inc. press release - Pfizer Announces Discontinuation of Phase III Clinical Trial for Patients with Advanced Melanoma] ]

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