94-04-28 UVa have identified a molecular cancer marker or peptide EMBARGOED UNTIL 6 P.M., EST, THURSDAY, APRIL 28 Contact: Marguerite Beck CHARLOTTESVILLE, Va., April 29 -- Findings published in today's Science may bring researchers one step closer to developing a vaccine that would harness the body's own immune system to fight a form of cancer. For the first time scientists at the University of Virginia have identified a molecular cancer marker or peptide that is recognized by the immune systems of multiple patients suffering from melanoma, a serious form of skin cancer. With the identification of this peptide, U.Va. researchers have homed in on the specific part of the melanoma cell that stimulates the body's immune system to attack and kill the cancer. Researchers extracted peptides off the surface of melanoma and analyzed them with tandem mass spectrometry to determine their chemical structure. Using methods developed at U.Va. by chemistry professor Donald Hunt, the researchers discovered which of the more than 10,000 peptides present on each cell would trigger the body's immune response. "By isolating a peptide that the immune system actually sees on the cancer cell surface, we are better able to understand the body's immune response to melanoma and hopefully harness it for treatment," said Dr. Craig Slingluff, assistant professor of surgery at U.Va. and co-investigator of the study. Normally, cells transport to their outer surfaces fragments of each of the thousands of proteins they are manufacturing at any given moment. These protein fragments are called peptides. Should a cell become infected by a virus, a few foreign peptides of viral origin will be mixed in among the thousands of normal cell peptides on that cell's surface. These foreign peptides elicit a response from the body's immune system, which leads to the destruction of the infected cell. Although melanoma is not caused by a virus, these cancer cells also generate melanoma-specific peptides that stimulate the immune system to attack the tumor. For reasons not yet understood by researchers, the immune response is often insufficient to kill the tumor while it is still in the body. Until now, the strategy used for melanoma vaccines has been to remove tumor cells from a patient with advanced melanoma, modify it in some way to get a stronger immune response and inject it back into the same patient. "The problem with this approach is that you must wait until the patient is in the advanced stages of the disease to be able to extract enough tumor cells to make a vaccine, and that vaccine will work only for that individual patient," said Dr. Victor Engelhard, professor of medicine and microbiology. "Peptides are a more convenient vehicle to deal with than a tumor cell. We now have an approach to treating people from whom there is no possibility of isolating a tumor. Another advantage is that we can make about a gram of this peptide in the lab in about 24 hours -- enough to potentially treat hundreds of people." The peptide isolated by U.Va. researchers is present in about 40 percent of the Caucasian population, which is at the highest risk for melanoma. "For the remaining 60 percent," Engelhard said, "we will need to identify additional melanoma-specific peptides." Researchers at U.Va. hope to begin clinical trials using this peptide within the next several months. More information: Dr. Victor Engelhard 804-924-2423 or 804-924-1706 Donald Hunt Ph.D. 804-924-3610 or 804-924-7994 [Submitted by: (cab2j@dmt03.mcc.virginia.edu) 28 Apr 94 15:14:07 EDT]