Cancer vaccines: Pursuing the promise

Can immunotherapy aid the war against women's cancers?
By Richard Saltus

With experimental treatments, even a glimmer of success may hint at larger gains ahead–especially as they're often tried first in those for whom all else has failed. With this in mind, Women's Cancers Program scientists remain optimistic about therapeutic cancer vaccines despite their infrequent successes in early clinical trials.

Taking heart from a few responses to a vaccine for ovarian cancer, the researchers hope to figure out the intriguing pattern of hits or misses to guide them as they move forward with an array of new strategies.

Like vaccines that have saved millions of lives by preventing smallpox, polio, and other infectious killers, cancer vaccines try to exploit patients' own natural defenses–the immune system. If this network of specialized white blood cells and tissues can recognize and destroy foreign microbes and viruses, why can't it be turned against life-threatening cancer cells?

It's an attractive idea that has been tested in many forms of cancer, but getting cancer vaccines to work is no simple matter because the intricacies of the immune system aren't completely understood. So far, these vaccines have fallen short of expectations in the clinic.

Beginning in 1999, a vaccine developed in the laboratory of Glenn Dranoff, MD, was administered to 41 Dana-Farber/Partners CancerCare patients with advanced ovarian cancer–a disease with a high mortality rate. The vaccine, marketed under the name GVAX by Cell Genesys, is a genemodified, irradiated, whole-tumor vaccine. To make GVAX, cells removed from the women's tumors were grown in a laboratory dish, genetically modified to stimulate the immune system, and injected back into the patients. The scientists hoped that the activated immune system would react against antigens (distinctive proteins) in the vaccine and attack any cancer remaining in the body.

While most patients had strong immune reactions to the vaccines, in general there was little clinical benefit. "If someone had a large amount of disease, we didn't see it go away with vaccination," says Marcus Butler, MD, a WCP scientist who directed the trial. However, there were intriguing exceptions: Two women who'd had surgery for recurrences of ovarian cancer mounted strong immune reactions and have been in remission for two and three years, respectively. That's highly unusual for patients in such advanced stages of the disease.

"It's encouraging," says Dr. Butler. "If we hadn't done this experiment, I have no doubt that these two patients' diseases would have progressed."