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May 26, 2005

Experimental human monoclonal antibody shows striking benefit in patients with advanced melanoma

Topics: Skin Cancer

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. It seems that Pfizer may now have a monoclonal antibody that can do exactly that - block the function of CTLA-4 and cause both regression and elimination of advanced melanoma, and continue working as an imunopotentiator and possibly offer protection against re-occurrance. The study was conducted at the M.D. Anderson Cancer Center in Houston, Texas.

Of 39 patients given a single injection of CP-675,206 (known as CP-675), tumors disappeared in three patients, shrunk in a fourth patient, and cancer stopped growing in five other patients. These responses have remained since their initial treatment, which ranged from 13 to 28 months ago.

Most of the patients in the trial had advanced melanoma, which has a median survival of less than a year, says the study's principal investigator, Luis Camacho, M.D., MPH, assistant professor in the Department of Melanoma Medical Oncology.

The researchers gradually increased the amount of the initially tested dose by 1,500 fold, evaluating seven different dose levels, before they found higher doses that both produced an effect and had tolerable side effects. Most of the patients who did not respond to the drug were those treated with the lower doses

The investigators report that CP-675 acts by blocking cytotoxic T lymphocyte-associated antigen 4 (CTLA4). The antibody, in turn, stops the function of CTLA4(Cytoxic T-lymphocyte associated protein 4), which functions as an immunosuppressor.

Like a vaccine, CP-675 seems to continue to work long after patients receive the single two- to four-hour injection. The investigators believe that the monoclonal antibody enlists the immune system to fight any new cancer cells trying to grow." The antibody may work particularly well in melanoma because previous research has shown the immune system, if activated, can recognize this cancer.

Based on the results, Pfizer has launched a Phase II study, which is enrolling 100 patients at seven institutions nationwide.

Cross posted by Hyscience

Posted by Richard at May 26, 2005 6:51 PM


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