Every day of our lives, our bodies' defenses mobilize to fend off infection. When we encounter foreign substances such as viruses and bacteria our immune systems send an army of white blood cells into battle to attack and destroy the invaders. Researchers are now applying what they've learned about this type of defense mechanism to activate the immune system against cancer. One group of investigators, led by Dr. James W. Young of MSK's Bone Marrow Transplant and Clinical Immunology Services, is exploring ways to arm a specific type of white blood cell called a "dendritic cell" so that it can prompt other white blood cells to attack and kill cancer cells. There are many types of white blood cells, each with its own shape, size, and function. Dendritic cells, which have treelike branches projecting from their bodies (the Greek word dendron means tree), make up no more than 1 percent of all white blood cells in the body. But despite their scarcity, they exert a powerful influence over immunity: They're at least 100 times more potent than other white blood cells in inducing an immune response. Dr. Young and his colleagues, including Dr. Ralph Steinman of The Rockefeller University (where Dr. Young first began this research), are exploring how to harness the power of dendritic cells. One type of immune response begins with another kind of white blood cell called a T cell. A resting T cell has the capacity to recognize a foreign invader, but it must be activated to do so. That's where dendritic cells join the battle. Dendritic cells are present everywhere in the body except the brain. When a virus, for example, infiltrates the body, it produces proteins called antigens that may attach themselves to dendritic cells. The dendritic cells then move into areas where T cells are waiting such as the spleen or lymph nodes and activate certain T cells to respond to the viral antigens. The newly activated T cells then travel through the bloodstream to attack the virus, wherever it may be lurking. Like viruses, cancer cells also produce specific antigens. In theory, it may be possible to equip dendritic cells with antigens against cancer cells, prompting the body's T cells to mount an assault against them. Dr. Young and his colleagues -- including MSK's Dr. Paul Szabolcs, of the Department of Pediatrics, and Dr. Malcolm A.S. Moore, incumbent of the Enid A. Haupt Chair of Cell Biology -- have learned how to remove immature blood cells from the body and multiply them into dendritic cells in the laboratory. This feat requires the help of special proteins called growth factors. With Dr. Michel Sadelain of the Department of Human Genetics, and Dr. Alan N. Houghton, Program Chairman for Immunology and Chief of the Clinical Immunology Service, Dr. Young is also investigating how to arm dendritic cells with cancer antigens. They are currently defining and refining the methods necessary to do this. "We hope to attach cancer antigens to dendritic cells, return these cells to a patient's body, and get them to activate the patient's T cells to destroy cancer cells," said Dr. Young. "And because the T cells would in many instances only recognize and attack the cancer cells, healthy cells would be spared, making this treatment more precisely targeted." Within the next couple of years, the approach may be applied to treating patients with melanoma and leukemia. It may also prove useful in preventing or treating infections that can develop in bone marrow transplant patients, whose immune systems are very fragile. Properly armed dendritic cells may also be useful in reducing the risk of graft versus host disease in transplant patients a condition in which the new marrow attacks the body of the recipient.
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