MADISON - By mimicking Nature's way of distinguishing one type of cell from another, University of Wisconsin-Madison scientists now report they can more effectively seek out and kill cancer cells while sparing healthy ones.

The new tumor targeting strategy, presented today (March 25) at the annual national meeting of the American Chemical Society, cleverly harnesses one of the body's natural antibodies and immune responses. "The killing agent we chose is already in us," says UW-Madison chemistry professor Laura Kiessling, who led the work with postdoctoral researcher Coby Carlson. "It's just not usually directed toward tumor cells."

In a series of cell-based experiments, the researchers' system recognized and killed only those cells displaying high levels of receptors known as integrins. These molecules, which tend to bedeck the surfaces of cancer cells and tumor vasculature in large numbers, have become important targets in cancer research.

In contrast, an established tumor-homing agent linked to the cell toxin doxorubicin destroyed cells even when they expressed very little integrin, indicating this strategy has the potential to kill cancerous and healthy cells indiscriminately.

"This study suggests that the cell recognition mode we used can direct an endogenous immune response to destroy cancer cells selectively," says Kiessling. "We think this could lead to a new class of therapeutic agents not only for cancer but also for other diseases involving harmful cells."

Cancer cells typically display higher levels of certain receptors on their surfaces than do normal cells, a fact that allows scientists to pinpoint tumor cells lurking among the body's scores of cell types. A popular approach employs a cell-binding agent, such as a monoclonal antibody, that is powerfully attracted to the target receptor and holds fast to any cell displaying it.

Although this strategy has benefits, it's not natural, says Kiessling. Cell recognition in
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Contact: Laura Kiessling
kiessling@chem.wisc.edu
608-262-0541
University of Wisconsin-Madison
25-Mar-2007