A Vaccine for Colon Cancer

A new approach to preventing cancer teaches the immune system to seek and destroy emerging tumors.

A cancer vaccine with a twist is making headway in clinical trials at the University of Pittsburgh School of Medicine. Rather than targeting a cancer-related virus–the way Gardasil targets human papillomavirus to prevent some cervical cancers–the new vaccine triggers the immune system to attack a faulty protein that’s often abundant in colorectal cancer tissue and precancerous tissue.

Colon cancer: This x-ray image shows a barium enema in a patient with cancer of the bowel.

The Pitt investigators say that if the vaccine is successful, it could potentially obviate the need for repeated colonoscopies in patients at high risk for developing colorectal cancer. These patients have had multiple precancerous polyps, called advanced adenomas, in their intestines, and they are routinely screened by colonoscopy for signs of recurrence.

The vaccine has already proven safe in patients with advanced pancreatic cancer. It is now in clinical trials to gauge the immune response it elicits in patients with a history of advanced adenomas. It works by spurring the body to manufacture antibodies against the abnormal version of a mucous protein called MUC1. While moderate amounts of the protein are found in the lining of normal intestines, high levels of a defective form of MUC1 are present in about half of advanced adenomas and the majority of colorectal cancers.

The vaccine primes the immune system to monitor the gut for emerging cancers by teaching it to recognize abnormal MUC1. If an adenoma develops and begins to produce the faulty version of MUC1, the immune system will raise antibodies to attack and destroy the precancerous tissue.

“You would be using your immune system as a surveillance mechanism to prevent the development of malignancy,” says principal investigator Robert E. Schoen, professor of medicine at the University of Pittsburgh School of Medicine and professor of epidemiology at Pitt’s Graduate School of Public Health.

Using this kind of immunotherapy to combat cancer isn’t new–a number of cancer vaccines are currently being tested in clinical trials. But so far the technique has been used only to attack existing tumors. The new vaccine represents the first attempt to use immunotherapy to keep cancer from forming in the first place. “This is taking it in a different direction,” says Schoen. “We’re now trying to use immunotherapy as a means of prevention.”

Not all colorectal tumors produce abnormal MUC1, and there’s no way to know ahead of time if a patient will develop one that does. So it’s still theoretically possible to develop colorectal cancer even if the vaccine is effective, says Schoen, because a vaccinated patient would still be at risk for tumors that don’t make faulty MUC1.

For that reason, it’s not clear yet whether the vaccine could supplant colonoscopies altogether in high-risk patients, says Mack Ruffin IV, professor of family medicine and a research scientist in epidemiology at the University of Michigan, who is not involved in the trials. “If they still need colonoscopies, we haven’t done anything but add extra cost and side effects to managing people with polyps.”

The Pitt investigators have been recruiting subjects for the trial since October 2008, and they expect to finish gathering data in fall 2011. Patients receive an initial dose of the vaccine with boosters 2 and 10 weeks later, and their immune response is monitored for a year. Because their history of advanced adenomas puts them at high risk for cancer, the patients are monitored throughout the trial with colonoscopies–the current gold standard for surveillance–giving the researchers a preliminary idea of whether the vaccine can limit recurrence or progression.

So far, in the more than 20 subjects already enrolled, says Schoen, “the vaccine is extremely well tolerated.” Beyond some redness and soreness at the injection site and the occasional short-term fever, there have been no adverse effects. The next step, Schoen says, will be another trial to determine more precisely the relationship between vaccine administration and adenoma recurrence. He estimates that those experiments could begin within two years.

Abnormal MUC1 isn’t limited to colorectal cancer. It’s also present in some other cancers, including most breast tumors, meaning the new vaccine could be adapted for other uses. More broadly, the strategy of stimulating the immune system to attack a tumor-related protein may be relevant for other types of cancer as well. Many proteins are known to be aberrantly expressed in malignant tissue, says Schoen, and “vaccines against other proteins could be used for other cancers.”

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