"All of the patients generated an active immune response to the vaccine, and the clinical results look very promising," says Kenneth A. Foon, MD, director of the Barrett Cancer Center at the University of Cincinnati College of Medicine, and an author of the report on the vaccine.

Cancer vaccines work much like traditional vaccines against infectious diseases, in which altered proteins from a "foreign" bacteria or virus are injected to act as antigens, which stimulate the immune system to attack any similar proteins found in the body.

One way the immune system stages this attack is by sending out proteins called antibodies that attach to the antigens, marking them for destruction by other immune system cells.

Virtually all colon cancer cells have an antigen covering their surfaces called carcinoembryonic antigen (CEA). Because an abundance of CEA is found on cancer cells, but normal tissue has none, CEA makes a good target for designing a therapy to zero in on cancer cells and leave normal cells unharmed.

The catch is that CEA is first present in colon cells during normal development of the fetus. As people get older, it disappears in normal tissue. If colon cancer occurs, the immune system may respond to CEA only weakly, since CEA is recognized as having once been a normal antigen in the fetus. This is called "tolerance," meaning the body won?t respond as strongly to CEA as it would to a bacteria, virus, or other protein that it sees for the first time.

Every antibody the immune system produces responds to only one kind of antigen, called an idiotype (from the Greek words, idio, meaning "one?s own" and typos, meaning "kind? or "type.") The antibody that responds to CEA is called the CEA idiotype.

Foon?s team made a protein in the lab that would attach itself to the CEA idiotype . It is different enough from CEA that the immune system does not mistake it for a normal body protein, but similar enough to CEA that the immune system attacks both it and CEA, killing cancer cells (because CEA resides on cancer cells). It is this "anti-idiotype," which mimics CEA in order to generate an active immunity, that is the basis of the colon cancer vaccine.

An initial, small clinical trial showed the vaccine produced an immune system response in 17 of 23 patients with advanced, metastatic (disease that has spread to other organs) colon cancer. In a second trial, all 54 patients given the vaccine after surgery to remove colon tumors had strong immune responses, including 33 who were also given the chemotherapy drug 5-FU ? which can hamper immune responses ? at the same time.

Trial participants were people who had had surgery and chemotherapy to remove their cancer but were still at risk for recurrence (who were lymph node positive, for instance); also included were those whose cancer had spread but was still isolated to one area (such as the liver). One vaccine recipient, whose cancer had spread to 22 lymph nodes by the time it was excised surgically, is living six years after surgery with no signs of recurrence; and another, whose disease had spread to distant organs, is alive five years after her last surgery with no evidence of recurrent disease. There was no other effective treatment available for several of the patients in this trial, and Foon calls the results "extraordinary."

Foon says a Phase III clinical trial of the vaccine will begin within a few months. It will enroll 1400 people, half of whom will get the standard chemotherapy agents, 5-FU and leucovorin; and, half of whom will get the chemotherapy plus the vaccine. Patients will receive regular vaccine boosts for up to five years, "to keep the immune system at peak level," says Foon. "The goal is relapse-free survival," he says. While excited about his early clinical trials, he looks forward to the larger Phase III trial results to be the definitive word on the vaccine?s effectiveness, he notes.

Foon also points out that since CEA is expressed on many other types of cancer tumors, the vaccine may not be limited to colon cancers. A lung cancer trial has recently begun testing the CEA vaccine in combination with other vaccines.

A cancer vaccine expert with the American Cancer Society (ACS), T. J. Koerner, PhD, agrees that Foon?s results among a small number of patients are "truly wonderful" but says much work remains to be done on cancer vaccines.

"This is good news about progress in getting a better immune response in colon cancer vaccines," says Koerner, director of research information management for the ACS. "There is hope this is a signpost pointing down the road to a time when these biological approaches may be available for ? and effective for ? a greater number of patients."

If the vaccine proves useful as a treatment, Foon says, he has suggested to the National Cancer Institute that it could be worth studying as a preventive measure for people at high risk for colon cancer. However, he says, it will take a much larger trial, with thousands of patients, to determine the feasibility, and at considerable cost.