Listeria inside a macrophage, an immune cell enlisted in the immune response. Credit: Paul Neeson, PhD, University of Pennsylvania School of Medicine
When bacteria such as Listeria and Salmonella are taken up into a phagocytic cell of the immune system, they are engulfed into a phagocytic vacuole in the interior of the cell. Here they may be destroyed and fragments of antigens they carry will eventually egress to the cell surface to activate CD4 immune cells, which are important in assisting in the immune response. Listeria, unlike other bacteria, has evolved to break out of the vacuole and survive inside the immune cell. This way antigens that Listeria carries are targeted to a pathway in the cytoplasm where they are broken into peptides and taken to the cell surface for recognition by killer T cells. These killer T cells seek out and destroy tumor cells displaying tumor-specific antigens. Credit: Yvonne Paterson, PhD, University of Pennsylvania School of Medicine
Findings Could Lead To New Immune Therapy for Breast Cancer
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.
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