Physician-scientists at Memorial Sloan-Kettering Cancer Center (MSKCC) are studying a novel approach to treat metastatic melanoma, known as immunotherapy, which uses the body's own immune system to attack cancer. Presented at the American Society of Clinical Oncology (ASCO) annual meeting, encouraging new data shows - for the first time - a survival benefit in metastatic melanoma patients using an immunotherapy discovered and clinically investigated by researchers at Memorial Sloan-Kettering.

The therapy, called anti-CTLA-4 (now known as ipilimumab), was developed in 1996 by James Allison, PhD, Chair of the Sloan-Kettering Institute's Immunology Program at MSKCC. For the past 20 years, Dr. Allison's research has focused on the mechanisms that regulate the immunologic responses of T lymphocytes - commonly referred to as T cells - with an emphasis on manipulating T cell response in order to develop novel tumor immunotherapy approaches.

Over the years, researchers from MSKCC have been deeply involved in preclinical and clinical studies using ipilimumab, most notably a 2009 Phase II multi-center trial led by Jedd Wolchok, a medical oncologist at MSKCC and participant in the Phase III trial (being presented at ASCO), which found a dose-response relationship to the drug in patients with stage III or IV disease. Dr. Wolchok also led a team in the development of a novel set of tumor-response criteria based on ipilimumab's unique mechanism of action.

Together, recent advances in understanding intracellular signaling pathways and immunotherapies such as ipilimumab to block those pathways have allowed clinicians to offer melanoma patients new treatment options for this disease.

"The success of ipilimumab is a milestone in cancer immunology and also in the development of more effective therapies for patients with advanced melanoma," explains Dr. Wolchok.

"This solid step forward in the treatment of metastatic melanoma could not have been possible without the insightful and visionary science of Dr. Allison, as well as the commitment of a team of dedicated colleagues at Bristol-Myers Squibb and a group of experienced and determined clinical investigators."

In addition, researchers at MSKCC are studying biomarkers to help identify those patients who could benefit most from therapies like ipilimumab, and they have received a National Institute of Health Grand Opportunity Stimulus award to study how the immune response to the NY-ESO-1 antigen is related to clinical outcome for ipilimumab therapy. This work, which is being conducted in several large clinical trials, is also supported by grants from the Melanoma Research Alliance and the Cancer Research Institute.

According to the National Cancer Institute, more than 68,000 new cases of melanoma were diagnosed in the United States in 2009, and more than 8,600 Americans died from the disease. Melanoma is the least common form of skin cancer, but is considered the most serious.

Source
Memorial Sloan-Kettering Cancer Center