Attacking tumors from within
Cancer-vaccine research advances at Dana-Farber
By Robert Levy
Vaccines developed by Glenn Dranoff, MD, are currently being tested against melanoma, lung cancer, ovarian cancer, and acute leukemia.
In Alfred Hitchcock's movie "Sabotage," a mild-mannered cinema owner attempts to terrorize London by shutting down the city's electrical system. Scotland Yard is slow to pick up his trail; he seems too ordinary to be a danger. Londoners themselves are more amused than frightened by the power outage. Slowly, though, a detective becomes suspicious of the shady figures visiting the cinema and decides to move in for an arrest. His action comes too late, however, as the owner has already sent off a bomb that explodes on a crowded bus.
Change the setting from London to the microscopic world of living tissue, replace the actors with human cells, and the film could be an allegory for the drama that takes place between cancer cells and the immune system, the body's defender against disease. If the immune system fails to detect and wipe out cancer cells, as it occasionally does, it is not because it's derelict in its duties, but because cancer cells blend in so easily with their neighbors. They behave, at least in their early stages, much like normal cells, giving few signs of their potential to become malignant.
Cancer cells can evade the immune system's radar because, in a real sense, they aren't alien to the body at all. A cancer cell is actually a normal cell — be it from the liver, breast, bone marrow, or other tissue — that has picked up some glitches in its genetic programming. The immune system, so proficient at finding and destroying truly foreign entities such as bacteria and parasites, often isn't sharp enough to detect the tiny, subtle differences that distinguish cancer cells from normal ones.
To use security parlance, cancer cells sometimes aren't attacked by the immune system because they don't "fit the profile" of a dangerous element. Rather than assault cancer cells and risk harming normal ones as well, the immune system seems to err on the side of caution — a restraint that, by allowing cancer cells to grow unchecked, can have life-threatening consequences.
All these facts have shaped the quest for new immune-based therapies against cancer — for vaccines that use the body's own diseasefighting forces as a weapon against tumors. Instead of trying to rev up or supercharge the immune system's response to tumors, which would risk damaging both healthy and diseased tissue, researchers are seeking ways of making cancer cells more conspicuous to the immune system.
At Dana-Farber, vaccine research has brought a shrewd ingenuity to the fight against cancer. Scientists using the tools of molecular biology are developing techniques that cause cancer cells to betray themselves as a potential enemy and, in effect, invite their own destruction.
Dana-Farber scientists are developing techniques that cause cancer cells to betray themselves as a potential enemy and, in effect, invite their own destruction.
The strategies for accomplishing this vary, but they all came about as a result of deepening understanding of how the immune system functions and interacts with cancer cells and other abnormal cells. Advances have been rapid; techniques that just a few years ago were being studied in the laboratory have begun to be tested in patients.
Although cancer-vaccine research was once the work of a few, relatively isolated scientists, it is becoming more of a collaborative venture in which investigators from different laboratories share findings and ideas. "Dana-Farber scientists are contributing to what may one day be seen as a revolution in vaccine research," says the Institute's Senior Vice President for Experimental Medicine Lee Nadler, MD. "There's a dynamism created by bringing together leaders in a particular field. We're poised to have an even greater impact in vaccine research as we move ahead."
Here, Paths of Progress surveys the main currents of cancer-vaccine research at the Institute.
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