Immunotherapy has revolutionized the way physicians treat cancer patients. Immunotherapy is a form of treatment that directs the patient’s immune system toward the tumor. This form of therapy aims to improve immune response specificity and efficacy. Scientists have used various methods to signal the immune system and target the tumor. Recently, work on engineered immune cells has gained a lot attention and promise within the clinic, however, other researchers hope to treat patients using different methods. Oncolytic virus treatment is one form of immunotherapy that provides promise to successfully target the tumor and improve patient survival.
Oncolytic viruses are a type of cancer treatment that uses viruses to infect and destroy tumor cells. In this therapy, viruses enter the tumor and use the tumor cells’ genetic mechanisms to replicate itself. Eventually, the cell will succumb, and the replicated virus will spread to other tumor cells. Specifically, in oncolytic virus therapy, the generated viruses can be engineered to reduce their ability to penetrate healthy cells. Additionally, once the oncolytic viruses destroy a cancer cell, it releases proteins or antigens that the immune system will recognize and use to target other tumor cells. While this treatment has been successful with one oncolytic virus treatment approved by the U.S. Food and Drug Administration (FDA), scientists are still working to improve tumor specificity and regression.
A recent paper in Nature Communications, by Dr. David Olagnier and others, demonstrated how a chemical drug, known as 4-octyl Itaconate (4-OI), enhances oncolytic virus treatment in cancer. Olagnier is Associate Professor in the Department of Biomedicine at the Aarhus University. His work focuses on immunological response to viruses and how to better improve oncolytic virus treatment to elicit an effective immune response.
Olagnier and others establish that various pathological responses to oncolytic virotherapy limit efficacy, particularly in the clinical setting. Unfortunately, treatment resistance can occur due to viral inhibition within the tumor, allowing cancer progression. However, a chemical drug that targets cellular inflammation was found to synergistically enhance an oncolytic virus in human and mouse treatment-resistant cells. The team used cells in a dish to mimic tumor mass and test the efficacy of the drug combination. The team discovered that 4-OI suppresses antiviral immunity in the cancer cells, which prevents the tumor from inhibiting the oncolytic virus. In this case, Olagnier and others discovered the intracellular pathways that are critical in antiviral immunity within tumor cells.
The work done by Olagnier and his team for the first time demonstrate that an antiviral drug enhances oncolytic viruses for cancer patients. They also identified the pathways within the cell that are inhibited to allow oncolytic virotherapy to work. This research is paradigm shifting as it becomes clear how we can improve immune response in oncolytic virus-resistant tumors. Combination treatment was successful in both animal and human cells, which further demonstrates the feasibility of treatment in the clinic. While more research needs to take place to confirm strong efficacy in humans, the initial findings provide hope that this new combination therapy will improve cancer patient survival and quality of life.
Paper, Nature Communications, David Olagnier, Aarhus University