That’s the question being investigated this spring at Lankenau Hospital, where 20 patients are taking part in a unique series of trials at medical centers all over the country. The drug they’re testing could well be a game-changing weapon in the ongoing war on cancer.
The person coordinating the trials is Dr. George Prendergast, president and CEO of the Lankenau Institute for Medical Research. Prendergast specializes in immunochemotherapy, the study of the immune system’s response to cancer.
Just as cancer evades the immune system and continues to grow, so does a fetus. “When a woman is pregnant, her immune system becomes dormant so it doesn’t harm the fetus,” explains Prendergast. “Specifically, the mother’s immune system doesn’t attack the fetus’s molecules from the father, which are foreign to the mother.”
The phenomenon is called immune tolerance. “It’s the same thing cancer does to the immune system—putting it to sleep, rendering it unable to attack the cancer cells,” Prendergast says. “The question is, can we turn it back on and get it to fight?”
Prendergast’s theories and research rest on IDO, a molecule that, when activated, shuts down the immune system. Turning on the immune system by turning off IDO is the goal of drugs being tested in clinical trials. “Cancer cells send signals to one another and to the rest of the cells in the body,” says Prendergast. “We’re trying to override that process and send a new signal directly to the immune system.”
IDO therapy could work on all kinds of cancer, says Prendergast. “And that’s another part of this that’s different. For decades, drug therapies have been introduced to fight specific variations of cancer cells. Many of those work, but some for only a certain period of time. The cancer cells mutate and regenerate. This [new] approach would enable the immune system to fight anything that cancer throws at it.”
The results of Phase I animal trials were so promising that the National Institute of Health granted $1.3 million dollars to Prendergast to conduct Phase II human clinical trials during the next five years. He was also named 2012’s “Inventor of the Year” by the Kimmel Cancer Center for his United States patent on IDO’s evil twin: IDO2, a second molecule that could be the culprit in allowing autoimmune diseases to invade the body.
“It’s a different gene that makes a different enzyme,” Prendergast says. “We believe it enables autoimmune diseases by throwing the immune system into disorder. IDO helps cancer by putting the immune system to sleep; IDO2 seems to do the same thing, but with autoimmune diseases. We want to turn IDO2 off so we can turn back on the immune system.”
Prendergast and the Lankenau Institute for Medical Research have had success with drug treatments targeting IDO2 and its response to rheumatoid arthritis. To continue that research, NIH awarded Prendergast a $400,000 grant to fund preclinical trials. “The work on IDO2 is in a much different place than that of IDO,” says Prendergast. “IDO is in drug trials. For IDO2, we don’t yet have a drug. We’re in the stage of researching IDO2’s behavior in regards to autoimmune diseases.”
Such research has raised another possibility: IDO and IDO2 could be in cahoots, collaborating to immobilize the immune system. “We did tests on IDO2 and pancreatic cancer, and there were preliminary links between it and that disease,” Prendergast says. “But again, we are a long way off from proving that—nor am I saying that there is a link between any autoimmune disease and cancer, or pregnancy and cancer.”
In truth, the drug therapies being investigated are years away from becoming realities. Such is the life of a medical researcher. Prendergast first had his IDO research confirmed in 2005. He started the Phase I trials in 2008 and is just now beginning the Phase II trials.
To Prendergast, however, this is rapid progress. “NIH approves only 5 percent of the grant applications it receives, so the fact that we got two of them for IDO and IDO2 research is huge,” he says. “We have the funds to move forward, albeit slowly. But if this works, it could change the way cancer is fought and killed.”
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