|Mol. mass||146380.472 Da|
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Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, there is also an inhibitory mechanism that interrupts this destruction. Tremelimumab turns off this inhibitory mechanism and allows CTLs to continue to destroy the cancer cells.
Tremelimumab binds to the protein CTLA-4, which is expressed on the surface of activated T lymphocytes and inhibits the killing of cancer cells. Tremelimumab blocks the binding of the antigen-presenting cell ligands B7.1 and B7.2 to CTLA-4, resulting in inhibition of B7-CTLA-4-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-CTLA-4-mediated inhibition.
On April 2, 2008, Pfizer announced that it has discontinued a Phase III clinical trial for patients with advanced melanoma after the review of interim data showed that the trial would not demonstrate superiority to standard chemotherapy. Studies for other tumors are planned as of October 2009[update], namely for prostate cancer and bladder cancer.
On October 4, 2011, MedImmune LLC gained worldwide rights on Tremelimumab to develop and commercialize the drug for treatment of cancer, while Pfizer retains all rights for combination therapies.
- Antoni Ribas (28 June 2012). "Tumor immunotherapy directed at PD-1". New England Journal of Medicine 366 (26): 2517–9. doi:10.1056/nejme1205943.
- Reuben, JM; et al. (1 Jun 2006). "Biologic and immunomodulatory events after CTLA-4 blockade with tremelimumab in patients with advanced malignant melanoma". Cancer 106 (11): 2437–44. doi:10.1002/cncr.21854. PMID 16615096.
- Pfizer Inc. press release – Pfizer Announces Discontinuation of Phase III Clinical Trial for Patients with Advanced Melanoma
- ClinicalTrials.gov NCT00702923 CP-675,206 in Combination With Short Term Androgen Deprivation in Patients With Stage D0 Prostate Cancer
- ClinicalTrials.gov NCT00880854 Study of CP-675,206 in Bacillus Calmette-Guerin (BCG)-Resistant Bladder Cancer
- Healthvalue.net: CTLA-4 Strategies
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