Duke researchers discover protein that can alert immune system to fi...( ely hiding from patrollingdendritic ce...)

ely hiding from patrolling dendritic cells, making cancer virtually invisible to the immune system, which can only mount a very weak response at best. The Duke researchers, led by Gilboa, have devised a way to engineer dendritic cells and grow them in the lab, and they have been testing various methods to prompt the cells to recognize cancerous tumors, thus targeting them for destruction.

Upon hearing that researchers at other institutions had successfully used GRP94 to mount an immune response, Gilboa and his colleagues launched a collaboration with Nicchitta, who had been studying the chaperone proteins for many years. Before long, the researchers had discovered that calreticulin is even better than GRP94 in stimulating the immune system. That work is the subject of the June 1 Journal of Immunology paper.

The finding prompted Nicchitta and his colleagues James Wassenberg and Cameron Dezfulian to examine just how a protein-folding chaperone might stimulate the immune system. Their findings are detailed in the July 1 issue of the Journal of Cell Science.

"To our surprise, we found that macrophages have a specific receptor on their cell surface that recognizes GRP94 and internalizes it," said Nicchitta. "The question is why would macrophages have a receptor on the exterior of the cell for a protein that is normally found only inside cells?"

Nicchitta speculates that the researchers have come across a previously unknown role for chaperone proteins.

The scientists are now trying to determine the pathway that antigen-presenting cells like macrophages and dendritic cells use to convert the molecular flags carried by chaperone proteins into a specific immune response.

Meanwhile, Gilboa and his colleague immunologist Smita Nair are beginning to explore the use of chaperone proteins as a basis for a new type of cancer vaccine.

"We are enthusiastic about the response we have seen to our v
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Contact: Karyn Hede
Hede0001@mc.duke.edu
919-684-4148
Duke University Medical Center
30-Jun-1999

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