Pitt researchers find promising candidate protein for cancer prevention vaccines
PITTSBURGH, Aug. 4 - Researchers at the University of Pittsburgh School of Medicine have learned that some healthy people naturally developed an immune response against a protein that is made in excess levels in many cancers, including breast, lung, and head and neck cancers. The finding suggests that a vaccine against the protein might prevent malignancies in high-risk individuals.
Mice that were vaccinated to boost their immune response against this cell cycle protein, called cyclin B1, were able to reject a tumor challenge in which they were exposed to a cancer cell line that overproduced it, explained senior author Olivera Finn, Ph.D., Distinguished Professor and chair of the Department of Immunology at the Pitt School of Medicine. The results are reported this week in the online version of the Proceedings of the National Academy of Sciences.
"Cyclin B1 is known to be produced in excess amounts in several kinds of cancer," she said. "While we were studying it, we noted that many healthy people already had an immune response, or antibodies, against the protein, even though they'd never had cancer."
According to the researchers, the immune response most likely developed during a childhood viral infection, when inflammatory responses are strong. Cells infected with chicken pox virus, for example, look very much like tumor cells because they, too, overproduce cyclin B1. The virus actually packages the host protein, which ultimately gets shown to the immune system as a marker of infected cells that must be destroyed.
"Because cyclin B1 is a 'self' protein, there have been concerns that boosting the immune response against it would produce autoimmunity and create new problems," Dr. Finn said. "But now that we know that perhaps 20 to 30 percent of people already recognize it as abnormal when made in excess, we can be more confident about the safety of a vaccine strategy to immunize high-risk groups against it."
She is working with collaborators to open, by the end of the year, a clinical trial of a cyclin B1 treatment vaccine in lung cancer patients, and she plans to assess it in the future as a prevention strategy in patients with pre-malignant lung lesions.
Natural immunity to other tumor-specific proteins has been found before, Dr. Finn noted. Her team developed a vaccine to boost response against MUC1, a protein that is abnormally produced in colon cancer and in precancerous polyps. The MUC1 colon cancer prevention vaccine is being tested in a clinical trial led by colleagues at UPMC.
"In previous work, we found that women who developed an immune response to MUC1, typically after pelvic surgery, mumps or mastitis, have a much lower risk for ovarian cancer," Dr. Finn said. "Cyclin B1 and MUC1 are part of a big family of self-proteins that become over-produced during cancer development, so they have great potential as targets in prevention vaccines."
Other authors of the paper include Laura A. Vella, Ph.D., and Min Yu, M.D., both of the Department of Immunology, University of Pittsburgh School of Medicine; and Steven R. Fuhrmann, Ph.D., Moustapha El-Amine, Ph.D., and Diane E. Epperson, Ph.D., all of the IOMAO Corp., Gaithersburg, Md.
The research was funded by grants from the National Cancer Institute Special Program of Research Excellence (SPORE) in Lung Cancer and the Dana Foundation.
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.