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News from the 2003 Clinical Congress
BREAST CANCER VACCINE INDUCES IMMUNITY IN PATIENTS AFTER TREATMENT FOR ADVANCED BREAST CANCER CHICAGO - A vaccine targeted against a peptide that is present in one out of three women with breast cancer has resulted in immunity for more than a year and a half in a small group of patients who generally have a high rate of disease recurrence after treatment. As reported at the 2003 Clinical Congress of the American College of Surgeons, in the first clinical trial of this vaccine, 12 patients were vaccinated, and all had a positive immune response. The immune response was durable, which means it persisted after patients stopped receiving the vaccine. It also was specific to the target antigen. "We can show that patients are not only responding appropriately in a global immunological sense, they also are generating a very selective vaccine response, which hopefully will carry forward to clinical responses such as less cancer recurrence," according to Craig D. Shriver, MD, FACS, director of the Clinical Breast Care Project at Walter Reed Army Medical Center, Washington, DC. Dr. Shriver explained that the trial is the first to demonstrate that the body can produce a uniform immune response to a distinctive aspect of cancer - the presence of the E75 peptide on the HER2/neu protein. "In all other models of vaccination, generating a specific immune response has been the key to the kingdom to developing a successful vaccination strategy." Other attempts to vaccinate patients with solid organ malignancies, such as breast cancer, have not even elicited a generalized immune response. "Even more important," Dr. Shriver added, "the immune response in our study approached a threshold which in other models is associated with an expected clinical response." This trial differs from trials of other types of cancer vaccines, such as those for renal cell carcinoma - which involves the kidney - and melanoma skin cancer. These trials included patients with a large volume of residual cancer after treatment. "We are studying the vaccine in patients who don't have active disease in an effort to prevent them from getting it," Dr. Shriver explained. The ultimate strategy will be to vaccinate women who have a high risk for developing breast cancer because of a family or personal history of the disease and other risk factors. "The last stage of testing the vaccine would be to vaccinate high-risk women who have never had breast cancer in an effort to prevent the disease from occurring in the first place," Dr. Shriver said. The vaccine tested by surgeons at Walter Reed Army Medical Center is directed at the E75 peptide, one of the epidermal growth factor receptors that are present on the cell surfaces of the HER2/neu protein. "Epidermal growth factor receptor acts like a fertilizer in many cancers. If patients have this growth factor, their tumors tend to grow faster and replicate at a higher-than-expected rate. So if you create a vaccine that blocks or destroys the E75 peptide, you may stop tumor cells from dividing faster or from dividing at all," Dr. Shriver explained. The vaccine also included granulocyte-macrophage colony stimulating factor (GM-CSF), a substance that stimulates bone marrow cells, to provoke a generalized response from the immune system. "GM-CSF was given to rev up immune system cells so that when these cells come in contact with the vaccine, they can produce a response that becomes part of the patient's native immune system response. Then, if any recurring cancer cells develop with an E75 peptide on the cell surface, the immune system will home in on them and destroy them before they get a foothold," Dr. Shriver added. The study included patients who were at high risk for breast cancer recurrence in a relatively short time because their disease had not been diagnosed until it had already spread to the lymph nodes. Breast cancer recurs in such women at a rate of 30 percent to 40 percent in five years. The vaccine was given to patients who showed no signs of breast cancer after they were treated with surgery, radiotherapy, or chemotherapy. A total of 35 patients were enrolled in the study, and 12 had tumors that expressed the E75 peptide on cell surfaces. These patients received six vaccinations of the E75 and GM-CSF vaccine in doses of 100 mcg, 500 mcg, or 1000 mcg. Patients had an immune system response to the vaccine if blood samples had increased numbers of immune system cells such as T-lymphocytes (immune system cells that control the spread of infected and malignant cells) and interferon-gamma-secreting cells (cells that regulate the inflammatory immune response) that were sensitive to E75. The patients in the study represent a minority of the women who have breast cancer in the United States. Because of screening mammography, most women with breast cancer in this country are diagnosed before disease invades the lymph nodes. To assess the effectiveness of the vaccine in a larger, more typical breast cancer population, Dr. Shriver and his associates have opened a clinical treatment trial in women with cancer that is confined to the breast. Over the next year, the surgeons will begin recruiting 100 patients for this trial. "We are putting more resources into this trial, which is a direct reflection of our excitement about the vaccine strategy," Dr. Shriver said. Dr. Shriver stressed that although the initial study indicated the vaccine produced long-term immunity against breast cancer, it is too early to determine whether immunity will translate into a positive clinical outcome, such as a lower rate of recurrence from breast cancer. Other researchers involved in the breast cancer vaccine trial include Jennifer M. Gurney, MD; Michael Woll, MD; Catherine Storrer, BS; Jeffery Gahan, BS; Lindsay Kotula, BA; Sathibalan Ponniah, PhD; and George Peoples, Jr., MD, FACS. # # #
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