A Vaccine For Breast Cancer?

SOMETIMES THE ONLY THING WORSE than having breast cancer is getting treated for it. Women with advanced illness often lose months to fighting the ravages of chemotherapy, and still their average survival time is less than a year. Scientists have long suspected that the immune system would make a better weapon, since it can kill diseased cells without harming healthy ones. But vaccine-style cancer treatments have proved an elusive goal. Now, after decades of preliminary lab work, several doctors are trying to immunize women against their own tumors. At least three therapeutic vaccines are now in clinical trials, and one of the most intriguing is a Canadian compound called Theratope. Last month the Food and Drug Administration authorized researchers at the University of Southern California to start testing the compound in 45 women with late-stage breast cancer. No one is touting it as a cure; in preliminary studies, the treatment has added only months to patients' lives. But it embodies a fresh approach to mobilizing the body's defenses.

The immune system is beautifully designed to repel foreign invasions. Antibodies and white blood cells roam the body, interacting with molecular markers, or "antigens." They attack any substance whose markings are unfamiliar. Though cancer cells are covered with unusual antigens, the immune system often ignores them. By grinding up cancer cells and mixing them with foreign material, such as dead or harmless bacteria, researchers can sometimes provoke a response.

Theratope is based not on minced cancer cells but on a single tumor-related antigen called STn. Michael Longenecker, the Canadian immunologist who developed the compound, has spent the past dozen years studying cellular structures called mucins. These treelike molecules protrude from the surfaces of healthy cells, protecting their soft interiors and helping them exchange chemical information. Researchers learned in the late '60s that the mucins on cancer cells are deformed. instead of abundant branches, they sport stubby, irregular twigs (chart). The STn antigen is simply a branch segment that wouldn't appear on a healthy cell. Longenecker and Dr. Malcolm Mitchell of USC hypothesized that if the immune system could be trained to attack STn, it might start attacking tumors.

Working with others at the Edmonton-based company Biomira, Longenecker first figured out how to synthesize STn in the lab. Then he joined the antigen to a protein called KLH to help ferry it through the body. Finally, working with Mitchell, he mixed the STn-KLH compound with a harmless bacterium. They named the brew Theratope and started testing it in animals and people. in a small human safety study, patients suffered no measurable toxic effects, and some improved. Of 13 women with widespread cancers, eight saw their tumors shrink or stop spreading, and two had mixed reactions (some tumors responded while others continued to grow). Only three patients those with the most advanced illness-failed to respond at all. As a group, the patients in the safety study lived an average of 20 months, nearly twice the usual duration.

It's a long way from there to curing cancer. But if the USC trial vindicates the mucin approach, Longenecker's team will have many other leads to follow. Even as the breast-cancer trial begins, British and Canadian researchers are testing the STn compound in people with advanced colon and pancreatic cancer. And Biomira has developed two related treatments, based on different segments of the mucin molecule. Longenecker hopes that by combining these compounds, and giving them to patients with less extensive illness, he'll get more dramatic results. Therapeutic vaccines are years from general use, and tomorrow's compounds may look very different. But the goal of harnessing the immune system appears more feasible than ever. "There has been a dramatic turnaround in the last few years," says Dr. Jean-Claude Bystryn of New York University. "This approach is now very much on the cutting edge." If immunotherapy fulfills its promise, some cancers may become as heatable as a bad flu.

A Vaccine For Breast Cancer? | News