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Vaccine Trial for Breast and Ovarian Cancer Enters Phase II

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Duke Health News 919-660-1306

DURHAM, N.C. -- Researchers at Duke University Medical Center are preparing to test a vaccine to see if it can prevent recurrence of breast cancer and ovarian cancer in up to one-third of women with these diseases. The physician-scientists have just finished the first phase of their novel clinical trial and are expected to enter phase II studies by the end of the year.

If they are ultimately successful, women whose cancer cells produce too much of what is known as the "Her-2/neu" protein might be able to take several doses of the vaccine to achieve life-long immunity to the cancer, a Duke researcher told participants at the American Medical Association's annual science reporters conference.

"This particularly aggressive kind of cancer often recurs even when treated with the most advanced clinical tools medicine offers. Our hope is that this offers a non-toxic way of finally shutting that cancer down," says Dr. Kim Lyerly, clinical director of the Duke Center for Genetic and Cellular Therapies.

According to oncologist Dr. Michael Morse, the trial's principal investigator, the first phase of the trial "showed the vaccine was safe and non-toxic in the six women it was tested in." The second phase will study the ability of the vaccine to stimulate immune responses in 25 women who have been treated for Her-2/neu breast or ovarian cancer and who either show no further evidence of cancer or who are in remission.

The FDA had approved the first phase of the trial, and their approval is expected shortly for the second phase. The trials are funded jointly by the National Institutes of Health and by Corixa Corp., a Seattle-based biotechnology company that holds a patent to the use of the Her-2/neu peptide for vaccination.

"This is potentially a more powerful strategy than a drug or chemotherapy can offer, because it is designed to give the body lasting protection against any cancer that displays Her-2/neu proteins," Morse said. In addition to 30 percent of ovarian and breast cancers, some gastric and lung cancers also are Her-2/neu positive, he said.

The Duke vaccine targets the same protein, Her-2/neu, as the anti-cancer drug Herceptin, which was approved by the FDA last month.

In a healthy cell, the Her-2/neu gene produces a protein receptor that sits on the surface of a cell. No one knows what this receptor normally attaches to but some believe it may be to a growth factor. In one-third of breast and ovarian cancers, this gene malfunctions, producing too many Her-2/neu protein receptors. The result is uncontrolled cell division and multiplication -- in short, cancer.

Scientists have found that they can eliminate cells with excess Her-2/neu receptors without affecting cells that express only a normal amount of the receptors. Eliminating these "over-expressors" kills the associated cancer. But Herceptin and the Duke vaccine differ in the way they go about doing this.

Herceptin is a monoclonal antibody produced in humanized mouse cells that sticks tightly to the Her-2/neu protein receptors, thus inactivating the cell. In that way, Herceptin mimics the body's own B-cell immune system: it uses a mock white-blood antibody that inactivates a cell. Thus, scientists generally agree Herceptin can only wipe out cancer cells that exist at the time of treatment.

The Duke Her-2/neu vaccine, on the other hand, is designed to induce a cell-mediated immune response which confers "memory" into that patient's immune response. It treats Her-2/neu receptors as a foreign body, an "antigen" that is spied by immune dendritic cells, which then revs up T lymphocyte killer cells to destroy the invader.

To prime those vital dendritic cells, the researchers are using a strategy they also employ in six other ongoing Duke vaccine trials. They take a blood sample from patients to extract the rare dendritic cells, then use a specialized laboratory to amplify the number of dendritic cells available. They then mix millions of these cells with the Her-2/neu receptor peptide, contributed by Corixa Corp., in such a way that the dendritic cells display the receptor as an invading antigen -- this will signal and activate immune fighters to find and destroy the antigen. The vaccine is then delivered back to patients through intravenous delivery in four separate infusions every three weeks apart.

If the vaccine works as hoped, it will destroy Her-2/neu proteins whenever the receptors are made by the errant gene, Lyerly said in an interview. "This ongoing cellular immunity is the same kind offered by such childhood vaccines as those for rubella and measles. Any evidence of those viruses in someone who has received a vaccine against them will prompt the immune system to destroy it. We hope the same will happen to prevent any Her-2/neu cancer from forming in women who have already experienced it."

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