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

IDO appears to be a sort of linchpin; its a crossroads where a number of mechanisms, some of which are more powerful than IDO itself, come together, says Dr. Munn. Tregs, for example, are much more powerful than IDO. If you take a mouse and remove IDO, it compensates just fine. If you remove Tregs, the mouse dies. But if the tumor uses IDO to recruit and activate Tregs, that is a leverage point.

Therapies aimed at these new leverage points will be most effective when packaged with other emerging and existing treatments, he says.

The FDA has approved early clinical trials of the IDO inhibitor, 1MT, in coming months. A team, led by longtime collaborator Dr. Scott Antonia, hematologist/oncologist and co-leader of the Immunology Program at the H. Lee Moffitt Cancer Center and Research Institute, will begin phase 1 trials of 1MT in patients with lung and other tumors shortly. MCG is pursuing FDA approval to begin trials of the combination of 1MT and chemotherapy in breast cancer patients. Dr. Munn notes that while the IDO inhibitor seems to be a safe drug that doesnt cause autoimmune disorders in mice, it wont be used in patients with autoimmune disorders because it could worsen the disorders.

By combining IDO with chemotherapy, researchers hope to wipe the slate clean of the tumors manipulation of the immune response, says Dr. Munn. We have found that once the tumor gets a hold of the immune system, just giving an IDO inhibitor does not restore everything to normal. The tumor has too much influence on the immune system at that point.

Standard doses of chemotherapy reduce immune system function, creating a window where IDO likely can be more effective. That window may work for cancer vaccines too, which are still under study and getting mixed reviews. Recent reports indicate vaccines can actually increase the number of Tregs in mice with tumors, a problem when fighting cancer but a possible opportunity in which an IDO inhibitor m
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert

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