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Breast tumors in mice eradicated using cancer vaccine

(Philadelphia, PA) - A team from the University of Pennsylvania School of Medicine has shown that by using a cancer vaccine based on the bacterium Listeria monocytogenes, they can cure mice with established breast tumors. Cancer vaccines, which are more properly described as immunotherapy, work by boosting an immune response against tumor-associated antigens. Using Listeria, the researchers, led by Yvonne Paterson, PhD, Professor of Microbiology, delivered the tumor-associated antigen HER-2/Neu to immune cells. HER-2/Neu is overexpressed in 20 to 40 percent of all breast cancers and also present in many cancers of the ovaries, lung, pancreas, and gastrointestinal tract. These cells eventually enlist killer T cells to seek out and destroy the tumor cells that display the HER-2/Neu molecule.

"We found that we can stop the tumor from growing out to 100 days, at which time we stopped measuring since this is a long time for experiments of this type," says Paterson. "The tumors stopped growing or went completely away." The researchers published their findings in the September 15 issue of the Journal of Immunology.

"The problem that we encounter is that often by the time a patient presents with cancer, they've developed immune tolerance to the tumor antigen, particularly when the antigen is expressed at low levels on normal tissue as with Her2/Neu," explains Paterson. "So how is the body to mount a strong enough immune reaction?"

In general, bacteria are good at inducing both innate and adaptive immune responses, activating such immune cells as macrophages, dendritic cells, and T cells. This helps jump-start the immune response to break tolerance.

But, why Listeria over other bacteria as a vehicle to deliver a tumor-associated antigen? Because of Listeria's unusual life style. Normally, when bacteria get taken up into an antigen-presenting cell, they are engulfed by a phagocytic vacuole where they get killedwhereupon their proteins get bro
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
14-Sep-2005


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