A bacterial mimic under study as a cancer vaccine because it signals the immune system to attack may also help some tumors hide, researchers have found.
Inside the body, the reagent - CpG oligodeoxynucleotides or CpG-ODNs - alerts the body's natural warning system to an invader, says Dr. Andrew L. Mellor, immunologist and director of the Medical College of Georgia Immunotherapy Center.
In an animal model, Dr. Mellor and his colleagues have found CpG-ODNs also can trigger a mechanism that may have helped the tumor survive in the first place: expression of an enzyme that enables it to hide from the immune system.
"What we have found is the ability to ring the alarm bell is a double-edged sword," says Dr. Mellor of new findings reported as a Cutting Edge article in the Nov. 1 issue of The Journal of Immunology. "The immunology community believes that the only thing these bacterial mimics do through the Toll-like receptors is ring the alarm bells to stimulate T cells to action. We are saying that if you deliver them in a certain way, they will also signal induction of the mechanism we have been working on which does exactly the opposite."
The mechanism is an enzyme, indoleomine 2,3-dioxegenase, that locally suppresses the immune response. MCG researchers reported in Science in 1998 that one way fetuses avoid rejection by the mother's immune system is expressing IDO, which degrades tryptophan, an amino acid essential to survival of T-cells, orchestrators of immune response. Since then, the researchers have found that tumors and some infectious agents, such as HIV, use this mechanism to escape the immune system.
In fact, Dr. David Munn, pediatric hematologist-oncologist, study co-author and Dr. Mellor's longtime research partner, is working with the National Institutes of Health on toxicity studies of an IDO inhibitor the researchers use in the lab with the goal of moving toward clinical studies of its potential to help cancer patients fight resistant tumors.
Dr. Munn says the treatment would likely be an adjunct to existing treatments, such as chemotherapy. Their newest study indicates the IDO inhibitor may also be a good companion treatment for the cancer vaccine that utilizes CpG-ODNs, says Dr. Mellor, a Georgia Research Alliance Eminent Scholar in Molecular Immunogentics.