Existing cancer vaccines for hepatitis B and the human papillomavirus aim to prevent the viral infections that can lead to liver and cervical cancers. But the experimental breast cancer vaccine aims to stimulate the immune response against breast cancer tumors themselves.
"With a vaccine approach to cancer therapy, cancer researchers hope to activate the immune system to target and destroy breast cancer cells while sparing healthy cells and tissues," said Michael DeGregorio, professor of hematology and oncology at UC Davis and principal investigator of the study. "We are investigating whether this particular vaccine has any impact on the development of breast cancer in mice when combined with anti-estrogen therapies, the current standard of care for patients."
Funded with a $3 million grant from Merck KGaA, the study is assessing the effectiveness of Stimuvax. The experimental vaccine targets MUC1, a cancer cell surface protein that is uniquely overexpressed in many cancers, including more than 90 percent of all breast cancers. Results from the UC Davis study will help direct the design of human clinical trials slated to begin worldwide in 2009.
"Hormonal therapies, such as tamoxifen or raloxifene, are FDA-approved for the treatment of breast cancer and for reducing the risk in women," said DeGregorio. "They work by blocking the action of estrogen, which is known to promote breast cancer development. But up to 20 percent of women with breast cancer choose not to go on anti-estrogen therapy due to quality-of-life side effects, such as hot flashes, insomnia and weight gain, in addition to life-threatening blood clots. The addition of a vaccine may enhance the effectiveness of these anti-estrogens as a prevention strategy."
For the study, DeGregorio and longtime collaborator Greg Wurz, a UC Davis research scientist, are assessing the vaccine's ability to prevent breast cancer in mice bred to promote human MUC1 expression and a gene known to spontaneously cause breast cancer. The mice additionally will be exposed to one of four anti-estrogen therapies to assess the vaccine's impact.
"We truly don't know all of the risks of hormonal therapies, especially when they are used as preventatives," said Wurz. "The fact that we're looking at a new treatment strategy that can be used much earlier in the disease process with potentially greater benefits and fewer negative outcomes is very exciting."
Ralph deVere White, director of the UC Davis Cancer Center, agrees.
"The results of these studies ultimately will help inform the cancer research community about whether it is possible to successfully integrate active immunotherapy into the standard of care for breast cancer," he said.
But beginning this summer, they will have an immediate impact on students who excel in the sciences at several high schools in rural Lake County. The grant will fund up to six research internships, giving students three-to-four weeks' experience in DeGregorio's state-of-the-art laboratory.
"As an alumnus of Kelseyville High School, I want to give back to the community," said DeGregorio. "By giving students first-hand experience in a research lab and showing them how scientists apply knowledge to find solutions to challenging health problems, I hope to help those who may be interested in pursuing a career in research or medicine."
Matthew Cockerton, principal of Kelseyville High School, appreciates the opportunity to expand students' knowledge.
"Opportunities like this don't surface for our school too often," he said. "Anytime we can give students real-world experience at a nationally ranked university, we are elated. And we are deeply grateful to Dr. DeGregorio for remembering his early experience and offering his laboratory to broaden our students' education."
DeGregorio leads the pharmacology research program at UC Davis Cancer Center, where he specializes in the molecular analysis of drug activity and the evaluation of biomarkers of drug response or resistance. The majority of his work focuses on developing new drugs that improve women's health.
"Vaccination strategies that engage the patient's own immune system in the fight against breast cancer are a growing area of research nationwide," said deVere White. "These studies are an important addition to our breast cancer program and our ultimate goal of discovering new and better treatments for our patients."
Information about the internships can be requested from DeGregorio by e-mailing him at mwdegregorio@ucdavis.edu.
UC Davis Cancer Center is a National Cancer Institute-designated cancer center that cares for 9,000 adults and children with cancer each year from throughout the Central Valley and inland Northern California. Its Outreach Research and Education Program works to eliminate ethnic disparities in cancer regionwide.