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Tumors use enzyme to recruit regulatory T-cells and suppress immune response
Date:8/16/2007

ight improve efficacy, Dr. Munn says. An antibody to the PD-L1/PD-L2 already under study in cancer may be another component of a total anti-tumor package.

We have data from a mouse model that while 1MT works modestly by itself, it works significantly better when combined with chemotherapy, says Dr. Munn. I think immunotherapy needs to learn from the finding with multi-agent chemotherapy, which is you need to orchestrate more than one approach. If you give one drug over and over again, the tumor invariably figures out a way to escape, so you always have to combine different strategies. Multiple approaches also reduce the chance of needing toxic levels of any of them.

Early clinical trials of the IDO inhibitor ideally will benefit patients for whom more standard therapies have failed and enable scientists to verify laboratory findings in people, Dr. Munn says. Scientists will carefully monitor Tregs to see if they show evidence of being activated by IDO now that they know what that looks like and de-activated by the IDO inhibitor. Theyll also have to see if Tregs circulating in the bloodstream are good indicators of whats happening or whether tumor biopsies will be needed.

IDO inhibitors potential against tumors as well persistent viruses such as HIV arose out of work MCG scientists, led by Dr. Munn and his long-time collaborator Dr. Andrew L. Mellor, director of the MCG Immunotherapy Center and Georgia Research Alliance Eminent Scholar in Immunogenetics. Their work published in Science in 1998 showed fetuses use IDO indoleamine 2,3-dioxygenase to locally disable a pregnant womans immune system and avoid rejection. They showed then that one way IDO suppresses the immune response is by degrading tryptophan, a natural amino acid important to T cells.

Later, they found that tumors and certain viruses such as HIV also appear to use IDO for protection from the immune response. However, the fact that IDO-expressing cells make up less
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert

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