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.

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.