One Vaccine, Many Targets

New treatments use cells' genetic makeup to locate cancer

Cancer researchers tend to be a skeptical bunch: They have seen too many promising lab results evaporate when tested in large clinical trials. Nevertheless, scientists and clinicians are dropping their guard a bit in reaction to a just-published report of a radically new treatment. In the March issue of Nature Medicine, a team of German doctors report that an experimental cancer vaccine eliminated tumors in 4 of 17 patients with late-stage kidney cancer, while the tumors in 2 others shrank by more than half--a dramatic success rate for a disease with a survival rate of less than 10%. And there were no toxic side effects.

Experts caution that the trial was extremely small: The results may not hold up when tested over a large number of patients. In addition, some other factor besides the vaccine may have played a role in shrinking the tumors. But "if these results hold up, it is really stunning," says Dr. Mario Sznol, an authority on cancer vaccines and vice-president for clinical affairs at Vion Pharmaceuticals Inc.

Such enthusiasm is prompted by the fact that the Germans, led by Dr. Alexander Kugler of the University of Guttingen, were able not only to prevent the spread or recurrence of tumors but also to reduce the size of existing tumors. "These were tumors you can actually see," says Dr. Allan Houghton, chief of immunology at Memorial Sloan-Kettering Cancer Center in New York. "They seem to have made these tumors go away. That's what's most remarkable."

PROMISE. The technology behind the vaccine, developed by Dr. Donald W. Kufe of Boston's Dana Farber Cancer Institute, can be used to customize a vaccine for many different cancers. Already, researchers at Beth Israel-Deaconess Hospital in Boston are enrolling patients for trials of a vaccine against breast cancer. And European trials are planned for liver and ovarian cancer.

There are other vaccines in the works as well, and the promising German vaccine trial boosts the profile for all of them. If enough of the vaccines prove successful, they may even bring about a critical shift in the way cancer is viewed. Because cancer vaccines seek out tumor cells by their biological makeup rather than their site of origin, "there could come a time when we no longer treat tumors based on their geographic location in the body, such as the lung or the breast," says Gail J. Mediris, president of Genzyme Molecular Oncology Corp. in Framingham, Mass., which is developing the core technology used in the Dana-Farber vaccine.

The buzz around vaccine research has been a long time coming. For almost 100 years, doctors have theorized that a vaccine made from a patient's own cancer cells could be used to stimulate the body's immune system to fight off tumors. It is only in the last decade, however, that vaccine research has come into its own. There are now 101 clinical trials under way for cancer vaccines at the National Cancer Institute, and dozens of biotech startups are developing vaccines that target a host of cancers (table). Experts in the field say that the first treatments could be approved in five to seven years.

Unlike vaccines for, say, measles, a cancer vaccine does not prevent the disease from occurring. Instead, it is typically used after surgery to prevent the tumor from recurring or spreading. The trick is to get the immune system to attack the deadly cells, a knotty problem, given that tumors are homegrown.

But some 20 years ago, scientists discovered bits of proteins on the surface of tumors, called antigens, that do not exist on healthy cells. A number of strategies have been developed to train the immune system's disease-killing T-cells to attack these antigens.

TOO BROAD? Most vaccines combine a few tumor-specific antigens with other immune boosting agents. The vaccine in the German trial veers off in a different direction: The doctors fused a whole cell from a patient's tumor to a dendritic cell, the white-blood cell that identifies foreign invaders to the T-cells. The fused cells contain all the proteins found in a tumor, on the theory that it is possibly more effective to attack multiple proteins rather than figure out specific targets. Some scientists argue, however, that the whole-cell approach may target too many proteins--good as well as bad--and they worry that healthy cells may be damaged in the long run.

Other new vaccines that target only specific antigens have turned in promising early results. At Cedars-Sinai Comprehensive Cancer Center in Los Angeles, researchers have high hopes for a vaccine made by Immune Response Corp. that is about to be tested against one of the most deadly forms of brain cancer. And several melanoma vaccine trials have produced outcomes almost as good as the German test.

At Memorial Sloan-Kettering Cancer Center, for example, a 1993 trial of a vaccine against late-stage melanoma is still bearing results: Rosemary Forbes, now 42, a mother of five living in South Salem, N.Y., remains in full remission seven years after receiving the vaccine, even though the cancer had spread to her lymph nodes and her prognosis was dire. "Both my father and my uncle died of melanoma, so it didn't look good," she says. "I feel very, very fortunate." Vaccine researchers hope we will be hearing more such testimonials in the next few years.

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