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Natural mechanism for immune suppression paves way for cancer trials

A natural mechanism pirated by tumors and HIV to evade the immune response is opening the door to better treatment for these conditions, researchers say.

The National Cancer Institute and Iowa biopharmaceutical company NewLink Genetics are pursuing FDA approval to move forward with cancer trials of a drug that inhibits the mechanism, an enzyme called indoleomine 2, 3-dioxegenase, or IDO, says Dr. Andrew Mellor, director of the Immunotherapy Center at the Medical College of Georgia.

The Georgia Research Alliance Eminent Scholar in Immunogenetics will deliver seminars about the biology and immunology of the mechanism at the Keystone Symposium on The Potent New Anti-Tumor Immunotherapies, in Alberta, Canada, March 28-April 2 and the World Immune Regulation Meeting April 10-16 in Switzerland.

Immune cells, particularly those in the mucosal surfaces of the gut, lungs and eyes, express IDO to mediate inflammation triggered by the constant assault of substances from outside the body.

Now, scientists know cancer in humans and mice also attract cells that express IDO, which degrades tryptophan, an amino acid essential to survival of immune system orchestrators called T-cells. MCG researchers are still exploring how IDO interacts with other cells to amplify immune suppression.

A team of MCG scientists, led by Dr. Mellor and his colleague, MCG pediatric oncologist Dr. David Munn, showed in 1998 that the fetus also expresses IDO to help avoid rejection by the mothers immune system. When they used an orphan drug known to suppress IDO in pregnant laboratory mice, fetuses were rejected.

The findings, published in Science, led the scientists to suspect and later prove that tumors and some viruses, including HIV, express it as well.

"Cancers should evoke a response from the immune system and dont," says Dr. Mellor. "That is a big question in the immunology field: Why dont they?"'"/>

Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
28-Mar-2007


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