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Breast cancer vaccine clinical trial to start soonBreast cancer news 3/9/2005 Researchers at Washington University School of Medicine and the Siteman Cancer Center in St. Louis are planning to proceed with a vaccine trial for breast cancer This vaccines stimulate immune cells to recognize tumor cells as foreign and destroy them. The target of the vaccine is called mammaglobin-A which is found in 80 percent of breast tumors. This protein is especially interesting for cancer immunotherapy because of its frequent occurrence and because breast tumors express it at high levels. In articles in the Journal of the National Cancer Institute and Breast Cancer Research and Treatment, the researchers report that researchers have constructed a vaccine consisting of copies of the DNA sequence that makes mammaglobin-A in humans. The researchers postulate that the DNA vaccine would rev up special immune cells called T cells to recognize mammaglobin-A as a foreign molecule when it is displayed on the surface of cells as an antigen.The primed T-cells then would proliferate and attack when they met with mammaglobin-A antigens. Mammaglobin-A is involved in breast development and is secreted in breast milk. Reserchers injected the DNA vaccine under the skin of test mice that had been engineered so that their immune systems would react to the human mammaglobin-A like a human immune system. The researchers loaded specific cells in the mice with mammaglobin-A antigens and found that the vaccine-primed T-cells attacked those loaded cells. The research team also transferred vaccine-primed T cells into mice with growing tumors that had or didn't have mammaglobin-A antigens. Tumors with mammaglobin-A antigens stopped growing and shrunk in volume, while those without the antigens continued to grow at the usual pace. The results of this experiment demonstrated that the vaccine-primed immune response is specific to mammaglobin-A antigens. Breast tumors with mammaglobin-A antigens on their surface also may display antigens that come from multiple parts of the mammaglobin-A molecule. Further experiments confirmed the importance of generating T cells that can react to a variety of different mammaglobin-A antigens. When the research team tested a DNA vaccine containing the DNA code for just one part of the mammaglobin-A molecule, they found T cells reacting to only that antigen, indicating that the method can generate immune cells that target specific parts of the mammaglobin-A protein. Now the researchers are planning to conduct clinical trials in patients who are at very high risk for breast cancer and in patients who have had a relapse after initial treatment. They want to see if giving patients the DNA vaccine can prevent or eliminate breast cancer or at least slow its growth. References: Narayanan K, Jaramillo A, Benshoff ND, Campbell LC, Fleming TP, Dietz, JR, Mohanakumar T. Response of established human breast tumors to vaccination with mammaglobin-A cDNA. Journal of the National Cancer Institute 2004 Sept 15;96(18):1388-1396. Jaramillo A, Narayanan K, Campbell LG, Benshoff ND, Lybarger L, Hansen TH, Fleming TP, Dietz JR, Mohanakumar T. Recognition of HLA-A2-restricted mammaglobin-A-derived epitopes by CD8 cytotoxic T lymphocytes from breast cancer patients. Breast Cancer Research and Treatment 2004; 88:29-41. Funding from the Susan G. Komen Breast Cancer Foundation supported this research. For more information Contact: Gwen Ericson jdryden@wustl.edu 314-286-0141 Washington University School of Medicine http://medinfo.wustl.edu |