Protective mechanism exploited by tumors may provide new cancer...( t a year before studies begin to look a...)

t a year before studies begin to look at the safety and efficacy of the treatments that would help make tumors more vulnerable to the immune system, Dr. Munn says. He added that the therapy likely would be an adjunct to existing approaches such as chemotherapy and possibly a tumor vaccine that stimulates the immune response.

"It's a general property of any tumor that survives long enough to come to medical attention that it has figured out a way to evade the immune system," Dr. Munn says. "What we would hope is that some group of tumors would rely primarily on this IDO mechanism to do that. It may not be because they are a particular type of tumor. It may be that tumors try different mechanisms and some breast cancers, colon cancers, melanomas or whatever hit on this particular strategy."

The idea of using this strategy against tumors began in 1998 when MCG scientists reported in Science that the fetus used IDO indoleamine 2,3-dioxygenase to locally disable the mother's immune system and avoid rejection. The potential of using the IDO mechanism to manipulate immune response is being explored in other areas as well, such as protecting transplanted organs from rejection and helping the immune system fight HIV infection.

Fortunately, several compounds that might inhibit IDO already existed, developed as part of studying pathways involving the natural amino acid, tryptophan. Tryptophan is a precursor to the neurotransmitter, serotonin, and some popular antidepressants work by making serotonin more available to the brain. IDO suppresses the immune response by degrading tryptophan, which also is important to T cells, major orchestrators of the immune response.

The MCG researchers were able to identify and isolate the IDO-expressing cells recruited by the tumor by using state-of-the-art cell-sorting equipment purchased for MCG by the Georgia Research Alliance. "Once we had them isolated, that allowed us to test them in vitro to see if t
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
15-Jul-2004

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