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Revving up the immune system to vanquish cancer

An unusual form of gene therapy to treat several forms of cancer is entering the second phase of human testing at Duke. The ultimate goal of the concoction is to help a person's immune system become its own best weapon to fight existing cancer and to protect itself against new cancer growth.

The new cancer vaccine, developed by doctors at Duke's Center for Genetic and Cellular Therapies, harnesses two biological powerhouses: the potency of rare immune cells, called dendritic cells, whose job it is seek out foreign tissue and alert the immune system, and RNA, the agent that transfers information from a cell's genome to the protein synthesis machinery of the cell.

The potential therapy just requires a sample of blood to extract the dendritic cells and a few cancer cells from which to distill RNA. Mixed together, the cancer-fighting cocktail produces everything the immune system needs to launch an attack on cancer.

Such a vaccine can be produced in an assembly line fashion, and in fact, a new cell processing laboratory at Duke is gearing up to produce mass quantities of this vaccine. Underthe leadership of surgeon Dr. H. Kim Lyerly, up to 100 patients may be enrolled in the second phase of testing the vaccine for breast, lung and colorectal cancers. The first phase of the trial, just completed, has shown that the vaccine is not only safe but can produce immune responses in cancer patients. Lyerly has also received federal Food and Drug Administration approval to start another phase 1 trial, using RNA extracted specifically from colon cancer cells.

Putting cancer in the hot seat

With six different on-going trials, Duke leads the country in the use of hyperthermia (heat treatment) for cancer. Hyperthermia uses microwave energy to heat a tumor mass so that radiation and/or chemotherapy can work better. It can be used for tumors deep in the body and has proven highly successful for ovarian cancer patients. It is now being used for women with advanced breast, head and neck cancers.

It is also helpful for superficial cancers. Some patients with malignant melanoma have so many tiny tumors on an arm or leg that doctors usually have little to offer. By ingeniously shunting the limb's major arteries and veins through a modified heart-lung machine, Duke surgeon Dr. Douglas Tyler increases the amount of chemotherapy a patient can tolerate up to 20 times higher than normal. The process also can heat the blood up to 102 degrees F, which increases the effectiveness of the chemotherapy. Doctors also are combining this treatment with tumor necrosis factor (TNF), a new, promising anti-cancer agent.

Glow-in-the-dark tumors

When doctors see a suspicious spot in a person's lung X-ray film or during a mammography, they usually have to order an invasive biopsy to tell if the spot is cancerous or is a benign tumor. Even when cancer is diagnosed, it is difficult to know if the cancer has spread or is confined to one tumor that can be removed surgically. And once a cancer is diagnosed, every hour counts to getting rid of it.

But physicians at Duke have pioneered a way to scan the whole body for cancer and when it is present, the cancerous cells light up like a Christmas tree. The technique uses PET imaging (positron emission tomography) and a sugar solution labeled with a radioactive tracer and injected into a patient's arm. When fast-growing tumor cells take up the sugar solution they literally glow. The technique allows doctors to accurately pinpoint cancers and determine the best course of treatment. And new research in Dr. Ned Patz's laboratory is developing even more specific imaging tracers that target specific subtypes of tumor cells, making diagnosis even easier. New life from afterbirth

Five years ago, umbilical cord blood was a shot-in-the-dark last chance for one young leukemia patient who couldn't find a matching donor for a bone marrow transplant. Today, Duke researchers think it holds promise for a broader spectrum of patients who otherwise would have no chance for life.

Like bone marrow transplant, cord blood initially was used in patients with blood system cancers. Now the treatment is used to replenish the marrow lost to patients of other cancers, including brain tumors, during extensive chemotherapy. And Duke doctors are finding new uses for cord blood every day.

"I look at cord blood transplant as a sort of 'poor man's gene therapy,'" says Dr. Joanne Kurtzberg, a hematology-oncologist who directs Duke's pediatric bone marrow transplant program. "By replacing a child's marrow, the blood producing and immune system, we are essentially able to change the genetic makeup. There are certain genetic diseases, like SCIDS, Krebbe and Hurler's diseases, that have been effectively treated through cord blood transplant."

Kurtzberg's research includes directing Duke's new cord blood bank, the third such facility in the nation, and taking cord blood treatment the next step - ex vivo expansion, or growing out immature cord blood cells in an incubator to produce a greater volume of blood and immune system cells for transplant patients.

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