November 2003

Booster Shot against Cancer

Cautious optimism about the latest efforts to enlist the immune system.

By Corie Lok

In the war on cancer, researchers have long struggled to recruit the body's immune system to attack tumors while leaving healthy cells alone. This strategy-basically that of vaccination-would offer a huge improvement over existing treatments such as chemotherapy and radiation, which kill healthy and diseased cells indiscriminately and carry harsh side effects. But repeated attempts to find a cancer vaccine have failed, largely because scientists have had a crude understanding of the molecular mechanics of the immune system and cancer cells.

Today, armed with a growing understanding of how to manipulate the immune system, researchers are offering the glimmer of a hope that cancer vaccines could soon become part of the cancer-fighting arsenal. More than 50 cancer vaccines are being tested in the United States, Canada, and Europe against several types of cancers, including melanoma and kidney, lung, breast, and prostate cancers. Several are in the final stages of human trials, at least two of which are expected to conclude within a year. In some of the trials, a few patients have seen their cancers go into remission, while in other patients, the vaccine slowed the spread of the disease. If all goes well, the first cancer vaccine could be ready for general use in three to five years.

"We are learning more and more about how to turn on the immune system and how to regulate it to get an antitumor effect. That's why we have so many potential new vaccines being pursued," says Antoni Ribas, an oncologist  developing a melanoma vaccine at the University of California, Los Angeles.

Cancer vaccines, unlike conventional vaccines, are designed not to prevent disease but rather to treat it. The immune system is normally relatively tolerant of cancer, and the trick is to get it to see tumors as the enemy. Approaches include manipulating tumor proteins and specialized immune cells in the lab, so that when they are put back into the body, they "teach" the immune system to see the tumors as foreign. Earlier attempts at cancer vaccines often used whole tumor cells, which present a mixed bag of unknown proteins to the immune system. Newer vaccines use a smaller number of extracted and purified proteins, which some researchers say promise to be more effective and predictable.

So far, successes have been modest but promising. One of the efforts that's gone farthest is a prostate cancer vaccine from Dendreon of Seattle, WA. In one trial, researchers found that a subset of patients with less aggressive tumors went a median of seven weeks longer than untreated patients before the disease progressed. A second trial focusing only on patients with less aggressive tumors is under way. If results are favorable, the company expects to file for regulatory approval with the U.S. Food and Drug Administration by late next year. Another company, Antigenics of New York City, is now conducting the final stage of human trials of kidney cancer and melanoma vaccines. The company expects initial results from the kidney cancer trial later this year.

At their most optimistic, of course, cancer researchers hope the new vaccines will stop and shrink tumors. That has happened in a few isolated cases in some trials involving melanoma and kidney cancers. But more likely is that these new vaccines will be part of a larger treatment strategy, a way to mop up cancer cells after surgery or chemotherapy, or to reduce the need for chemotherapy or radiation in the first place.