Vaccine could delay bowel inflammation and colon cancer, says Pitt research

PITTSBURGH, March 24 – An experimental vaccine against an abnormal protein found in some tumors has the potential to delay the onset of inflammatory bowel disease (IBD) and in turn prevent progression to colon cancer, according to researchers at the University of Pittsburgh School of Medicine. Their findings are reported this week in Cancer Prevention Research, a journal of the American Association for Cancer Research.

People with chronic inflammatory disorders such as IBD are at greater risk for developing cancer at the inflamed site, said senior author Olivera Finn, Ph.D., professor and chair, Department of Immunology, Pitt School of Medicine. In other cases, genes that develop cancerous changes can trigger inflammation. The vaccine made by her team is directed against an abnormal variant of a self-made cell protein called MUC1, which is altered and produced in excess in both IBD and colon cancer.

"Our experiments indicate that boosting the immune response against this protein early in the disease can delay IBD development, control inflammation and thereby reduce the risk of future cancers," Dr. Finn said. "These findings suggest also that the early stages of chronic inflammation might be considered a premalignant condition."

The researchers tested transgenic mice that spontaneously develop IBD and then progress to colitis-associated colon cancer, producing the human version of MUC1 in both disease states. They found that animals that received the vaccine showed the first signs of IBD significantly later than those in two control groups that did not get the vaccine.

Microscopic evaluation of the colon tissue showed less inflammation in the vaccinated mice, and no indication of cancerous changes. Nearly half of the animals in each of the control groups had evidence of abnormal tissue, and two had colon cancer.

"The MUC1 vaccine seems to change the local environment from one that promotes cancer development to one that inhibits it," Dr. Finn said. "Certain immune cells that we usually see in the inflamed colon aren't present, and that could make the surroundings less friendly for potentially cancerous cells that also are directly targeted by the vaccine for destruction."

This study suggests that in the future the vaccine might be considered as part of the therapeutic regimen for IBD as well. The experimental vaccine has been studied in patients with colon and pancreatic cancer and currently is being tested as a prevention measure in patients who have a high risk for developing colon cancer.

The study was funded by the National Cancer Institute and the Cancer Prevention Foundation.

The lead author of the paper is Pamela L. Beatty, Ph.D., University of Pittsburgh; co-authors include Sowmya Narayanan, University of Pittsburgh and Chatham University; Jean Gariepy, Ph.D., University of Toronto; and Sarangarajan Ranganathan, M.D., Children's Hospital of Pittsburgh of UPMC.

As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.