Lankenau Institute for Medical Research (LIMR) scientists published a teaching article for oncologists, physicians and health professionals to illuminate the basic research findings of the human immune system function and its application to treating cancer more effectively.
Some of the most heralded stories coming out of cancer research in recent years involve immunotherapies. These novel therapies harness the power of the human immune system to recognize cancer cells as foreign and prompt immune cells to kill the cancer. Many immune-system targeting medications have been approved for use in patients with melanoma, prostate cancer and certain types of lung cancer, and several more currently are in clinical trials. The medical excitement is centered around their ability to improve survival in some patients with advanced and aggressive cancers.
New therapies come so quickly that some oncologists may have trouble staying informed about the current targets of immunotherapy. With that need for information in mind, three experts from LIMR, which is part of Lankenau Medical Center (LMC) and Main Line Health (MLH), authored a manuscript that reviews the basic mechanisms of natural immune responses as well as the latest news related to therapeutic agents. Physicians who read the article also can go online and take a test to assess their learning and gain “Continuing Medical Education” credits, an honor provided only to specific articles published that are independently recognized as physician-training tools.
“Physicians who prescribe these newer drugs might observe their profound therapeutic effects but might not have had easy access to the immunological progress made during the past decade that has led to an understanding of the mechanisms of action and how that progress has been translated into anticancer activity,” wrote the authors Jonathan and Gerald Messerschmidt and George Prendergast, PhD, in their manuscript published in a recent issue of the medical journal The Oncologist.
Dr. Prendergast is the president and CEO of LIMR, and Gerald Messerschmidt, MD, is the director of the Clinical Research Center at LIMR. His son, Jonathan Messerschmidt, is a biochemistry and molecular biology student researcher at Boston University, and a former member of the LIMR immunotherapy laboratory, headed by Laura Mandik-Nayak, PhD.
IDO1 and IDO2
In addition to discussing the new immunotherapy drugs on the market, the authors described the mechanism of action of IDO (short for indoleamine 2,3-dioxygenase), an enzyme that is over-expressed in many types of cancer. It is thought that IDO turns off an immune response to tumor cells. Therefore, suppressing IDO expression may be a way to fight cancer.
“In its normal state, IDO appears to act to protect against an overactive immune system,” wrote the authors. For example, it helps stop a mother’s immune system from viewing a fetus in a mother’s uterus as a foreign agent and destroying it. Dr. Prendergast and his team began looking at IDO suppression as a possible cancer preventative more than 10 years ago. They found that many cancers activate IDO, making use of its braking function so as to evade immune attack of the cancerous cells.
LIMR researchers discovered a second IDO gene, IDO2, which lies just downstream (on chromosome 8) of what is now called IDO1 and may be the critical element to immune behavior. “Our study concluded that it was IDO2, not IDO1, that is crucial to the production of autoantibodies and autoimmune disease,” wrote the authors. “These data are crucial to understanding how tumor cells are able to escape the immune response. By further understanding the mechanisms of self-recognition and immune evasion, researchers and clinicians can work together to prolong the lives of patients.”
The authors noted that three IDO-pathway inhibitors are in clinical trials to determine their effectiveness in treating breast, prostate and other cancers. They concluded that the new classes of immunotherapy drugs may prove useful in restoring the patient’s own natural immune capacity to battle cancer development.