Not Just for Prevention Anymore

By Frederic Golden

Think vaccines: a quick needle in the arm or buttock to ward off flu or measles, right? Not necessarily. Most of the vaccines being developed today are designed to treat disease, not prevent it. "The field is exploding," says Dr. Jeffrey Schlom of the National Cancer Institute (NCI), sponsor of nearly 100 studies of therapeutic vaccines, many of them to fight melanoma, a deadly skin cancer.

Like their predecessors, therapeutic vaccines stimulate the immune system. But there is a key difference. Instead of targeting invading viruses or bacteria, they mobilize the body against a homegrown menace: cells growing wildly out of control, usually as the result of a spreading cancer.

For years doctors tried to stir immune reactions against cancers with a weakened tuberculosis bacterium called bacille Calmette-Guerin (BCG), but had only middling success. What has given the old idea a shot in the arm, so to speak, is biotechnology. Researchers like NCI's Dr. Steven Rosenberg have been able to isolate fragments from the surface of melanoma cells. Injected into the body, these antigens trick the immune system into producing a flood of killer T cells, which then go after the tumor cells containing the telltale fragments.

Other cancers are also being targeted. In July doctors at the University of North Carolina began trials of a breast-cancer vaccine based on bioengineered dendritic cells--rare white blood cells that act as scouts for the immune system. These lock onto a protein called HER-2/neu found in the tumors of a third of all breast cancers. At UCLA's Jonsson Cancer Center, researchers are working on a vaccine to treat brain cancer. Still other scientists are experimenting with vaccines for kidney, colon, pancreatic and ovarian cancer.

In perhaps the most novel vaccine, drugmakers at Progenics Pharmaceuticals and Cytogen are using viruses to deliver "naked" DNA directly into the body to fight prostate cancer. Containing the genetic instructions for making a common tumor protein called prostate-specific membrane antigen (PSMA), the DNA triggers a wholesale immune attack on all cells containing the antigen. Having succeeded in animal studies, the vaccine will soon move into human trials.

Besides AIDS and Alzheimer's disease, each the target of major vaccine research, vaccine designers are also eyeing autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, in which the body in effect attacks itself. At Israel's Technion, Dr. Nathan Karin and his colleagues have created genes that order up the culprit peptides--bits of protein that provoke the autoimmune response--then get the immune system to neutralize them. Says Karin: "Essentially, the process involves fooling the immune system into fighting itself."

--By Frederic Golden