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Researchers developing cancer vaccine
Wednesday, August 05, 2009

Researchers have learned that some healthy people naturally develop an immune response to a protein produced abundantly by colorectal, cervical, breast, lung, and head and neck cancers.

That finding has prompted a University of Pittsburgh School of Medicine team of researchers to develop a vaccine that shows promise in preventing malignancies in high-risk individuals.

Already tested in mice, the vaccine boosts immune response against the abnormal production of the cell-cycle protein "cyclin B1," making it possible for mice exposed to cancer cells that produce the protein to avoid tumor development, said Olivera J. Finn, chairwoman of the Department of Immunology at Pitt's School of Medicine.

Creation of an immune response before the mice were exposed to cancer "significantly delayed or completely prevented tumor growth," compared with mice in the control group that all died from malignant tumors, the study states.

Researchers found that "immunity elicited through a vaccine can inhibit tumor growth and significantly increase overall survival," says the study, published this week in the online version of the Proceedings of the National Academy of Science.

The vaccine succeeds because the cyclin B1 protein is more than just a byproduct of tumor growth. Dr. Finn said the protein that specific cancers generate at abnormally high levels is key to tumor survival.

But in an unexpected observation, the team found that many healthy people develop natural antibodies against the cyclin B1 protein even though they've never had cancer. The study also found no correlation between age and antibody levels in 65 people aged 20 to 75 whose blood was tested for natural levels of the antibody.

Development of the immune response likely occurred during childhood viral infections when inflammatory responses are strong. Dr. Finn said cells infected with chicken pox virus, for example, look very much like tumor cells because they also overproduce the cyclin B1 protein.

She's now working with collaborators to launch a human clinical trial on the anti-cyclin B1 vaccine in lung cancer patients. Future trials also could use the vaccine in a prevention strategy for patients with premalignant lung lesions.

Dr. Finn expressed confidence the vaccine will work in humans, as it did in mice, because cyclin B1 functions almost identically in both. "What we see in mice we are comfortable in assuming that the same will happen in people," she said.

The research team previously discovered a natural immunity to another tumor-specific protein.

Dr. Finn's team developed a vaccine to boost response against MUC1, a protein produced excessively in colon cancer and precancerous polyps. UPMC has a human clinical trial under way to test the MUC1 colon-cancer prevention vaccine. Recruitment of participants for that trial continues.

"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, she said, are members of a large family of proteins overproduced during cancer development, making them potential targets for prevention vaccines.

David Templeton can be reached at dtempleton@post-gazette.com or 412-263-1578.
First published on August 5, 2009 at 12:00 am
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