When the researchers looked into the lymph nodes where tumors drain typically the first place tumors spread they found a subset of normal host immune cells were expressing IDO, an immunosuppressive enzyme also expressed by the fetus to help avoid rejection by the mother's immune system.
They also found that when they gave a drug to block IDO expression, the immune system rallied.
"Our hypothesis in this situation was that the bad guys in this case were actually cells from the host, perfectly normal cells that had, in a sense, been requested by the tumor," says Dr. David Munn, pediatric hematologist-oncologist and lead author on the study published in the July 15 issue of Journal of Clinical Investigation.
Now they have shown in an animal model that these normal cells are a type of dendritic cell that was previously ignored by the scientists because they believed the cells were involved in making antibodies not in suppressing the immune system. By recognizing the actual role of these previously discarded cells, the MCG scientists and their collaborators have moved significantly closer to using this approach to help cancer patients.
"We have demonstrated that the IDO inhibitor drug is useful in mice," says Dr. Munn. "It's useful in a tumor model that is related to the kinds of patients we would want to treat. This brings us closer to being able to approach the FDA suggesting that IDO inhibitor drugs would be appropriate to use in patients."
The National Institutes of Health will do toxicity studies of the IDO inhibitor as well as other studies needed to take the proposal for clinical trials to the Food and Drug Administration, Dr. Munn says.
Should the FDA move toward clinical trials, it likely will be at leas
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
15-Jul-2004