Glioblastoma is a highly aggressive brain tumor with about a 10% 5-year survival rate. The debilitating disease affects roughly 3 people per 100,000. According to the Mayo Clinic Comprehensive Cancer Center, over 300,000 individuals worldwide are diagnosed with glioblastoma. Specifically in America, about 13,000 individuals are diagnosed with this less common cancer type. Those that are Caucasian and over 45-years old are at greater risk. Interestingly, glioblastoma tends to be slightly more common in men than women. The treatment for patients with glioblastoma is a multimodal approach that includes surgery, chemotherapy, and radiation therapy. The rise of immunotherapy – the enhancement of antitumor immunity – has also been introduced in preclinical research to improve patient survival.
Immune cells are critical for the body to fight off disease and chronic malignancies, like cancer. T cells are a main focus among scientists generating immunotherapy because of their specific ability to find infected cells and eliminate them. Therefore, many immunotherapy treatments function to generate a robust T cell response. Unfortunately, immunotherapy in more aggressive tumors, such as glioblastoma, have only modest effects. Many of the present immune cells around the tumor become dysregulated and are unable to function properly.
A recent article in Med, by Dr. David Tran and others, found that a new tiple therapy regimen with an immunotherapy, chemotherapy and Tumor Treating Fields therapy (TTFields) stunts glioblastoma growth and activates the body’s immune system. Tumor Treating Fields therapy uses low intensity, alternating electric fields that disrupt tumor growth by dysregulating intracellular structures. The novelty of this triple combination therapy comes from the multimodal approach – an immunotherapy, chemotherapy and TTFields. Specifically, both the TTFields and chemotherapy halt and reduce tumor growth through direct cancer cell death. Additionally, the immunotherapy activates T cells surrounding the tumor to further mitigate glioblastoma progression.
Tran is an Associate Professor of Neurological Surgery and Neurology, Division Chief of Neuro-Oncology, and Co-Director of the University of Southern California (USC) Brain Tumor Center (BTC) at the Keck School of Medicine of USC. His work focuses on understanding the mechanisms of how brain cancers develop, progress and resist treatment. Tran’s lab uses systems and computational analyses to conduct experiments and develop novel anti-cancer therapies that can be moved into the clinic.
TTFields was delivered through electrodes placed on the head for 18-hrs a day to obtain maximal benefit. Researchers discovered that TTFields attracts more T cells to the site of the tumor, which improve immunotherapy treatment. In this case, researchers are priming the glioblastoma with T cells that have the potential to eliminate rapidly dividing tumor cells. Chemotherapy was added to the regimen because of current clinical trials that combine it with TTFields. By adding immunotherapy with chemotherapy and TTFields, there was a 70% increase in overall survival. Additionally, patients with larger glioblastoma tumors responded better and had longer survival rates. Larger tumors were found to have more markers that activated T cells could target. Overall, this combination therapy enhances glioblastoma treatment and improves patient survival in aggressive tumors.
