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Breast tumors in mice eradicated using cancer vaccine

e where they get killed�whereupon their proteins get broken down into smaller pieces (peptides) and attached to MHC Class 2 molecules. These egress to the cell surface, where they expand and activate helper T cells, which are enlisted into the immune response.

But Listeria has evolved to escape from this vacuole and survive inside the cytosol of antigen-presenting cells, where it can replicate and grow, unlike other bacteria. So, although some of the bacteria are destroyed in the vacuole that feeds the MHC class II pathway of antigen presentation with the induction of helper T cells, others survive by escaping into the cytosol of the cell. This is important because the antigen-processing pathway that feeds antigenic peptides to the surface of the cell for recognition by killer T cells is generated in this cellular compartment. "We reasoned that if we could get Listeria to secrete a foreign protein into the interior of the cell, it would target that pathway and would elicit a strong killer T cell response, and we have shown that," says Paterson. "Listeria is almost unique in the bacterial kingdom in doing this."

In this model, pieces of the very large HER-2/Neu molecule are broken up into little fragments and bound to the MHC Class 1 molecule within the antigen-presenting cell. This is what the killer T cell "sees" at the cell surface. These killer T cells, which are being produced in the spleen, where Listeria usually colonizes, seek out and destroy the tumor. This system ensures an increase in the production of killer T cells that can recognize the HER-2/Neu pieces on the surface of the tumor cell. In addition, the Penn team helped the immune system along by fusing the tumor antigen to a bacterial protein that seems to activate antigen-presenting cells. They have found that by doing this the immune system now recognizes regions of the HER-2/neu molecule that are not immunogenic when presented by other vaccine approaches.

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Source:University of Pennsylvania School of Medicine


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