So far, the scientists' experiments reveal that calreticulin and a related protein called GRP94 both can alert the immune system by informing it about where in the body an insult has occurred. The proteins act as informants by carrying small pieces of cellular proteins called peptides as a type of calling card, with an address describing where in the body the injury is; for example, the skin or the thymus.
"The peptides appear to act as a fingerprint of the cell," Nicchitta said. "They tell the immune system where to marshal its forces. We are now using that property of these chaperone proteins to educate the immune system to fight cancer."
These molecular calling cards act as immune stimulating substances called antigens and are recognized by specialized immune system cells, either macrophages or dendritic cells. When these immune cells come into contact with calreticulin or GRP94, they appear to swallow the protein, release the peptides and display them on their cell surface. This display of a foreign peptide can trigger a strong response from immune system fighters known as killer T cells.
The Duke researchers showed that when they injected mice with dendritic cells that had been mixed with calreticulin or GRP94 purified from melanoma (skin cancer) or thymoma (thymus tumors), the animals responded by generating large numbers of killer T cells directed at the specific tumor type from which it had come.
"The immune response mediated by calreticulin is impressive," said Dr. Eli Gilboa, research director of Duke's Center for Genetic and Cellular Therapies. "This result shows the promise of this class of proteins to elicit a targeted cytotoxic T lymphocyte (killer T cell) response to tumor tissue."
Tumor cells have evolved ways of effectiv
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Contact: Karyn Hede
Hede0001@mc.duke.edu
919-684-4148
Duke University Medical Center
30-Jun-1999