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Duke scientists overcome immune resistance in dendritic cell vaccines for cancer

DURHAM, N.C. -- Scientists have discovered why dendritic cell vaccines do not attack cancer as forcefully as expected, and they have demonstrated how to overcome this constraint by bolstering the vaccines' tumor-seeking machinery.

The findings, published in the April 4, 2004, issue of Nature Immunology, present a novel method of equipping dendritic cells so they can activate the immune system to fight against cancers, said the researchers from the Duke Comprehensive Cancer Center and the departments of medicine and immunology at Duke University Medical Center.

Dendritic cells are the "private investigators" of the immune system, detecting foreign proteins in the body -- for example from bacteria and viruses -- and presenting them to "fighter" T-cells for destruction. Scientists turn dendritic cells into cancer vaccines by mixing them with genetic material from the patient's tumor and infusing the treated cells back into the patient. The dendritic cells present the tumor particles called antigens to the fighter T cells, as though pointing out the enemy to a battalion of soldiers.

"Dendritic cell vaccines have shown promise in battling cancers in laboratory studies, but they have not met with quite the success in the clinical trials that laboratory studies suggest they should," said Yiping Yang, M.D., Ph.D., assistant professor of medicine and immunology, the lead author and principal investigator of the study. "Our study highlights what element is missing in dendritic cell vaccines that prevents them from activating the immune system, and we've shown how to insert that element."

The major problem, said Yang, is that cancer cells are wily invaders, camouflaging themselves as part and parcel of the body in order to escape detection by the immune system. Dendritic cells present the tumor antigen to T-cells, yet T-cells are curiously tolerant to the antigen and fail to act on its threat.

Yang and his team studied why this toleran
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Contact: Becky Levine
levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
4-Apr-2004


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