There are some promising advances in treating glioblastoma and other cancers with immunotherapy.
The most frequently diagnosed type of brain cancer in adults is glioblastoma multiforme. Despite the emergence of immunotherapeutic approaches for a number of cancers, reliable treatments that can extend overall survival of patients with glioblastoma to the two-year mark and beyond are still under investigation. There are some promising advances such as an experimental dendritic cellbased vaccine that increased the median overall survival rate from 15 months to 23 months.
The toughest challenges to overcome in treating brain tumors is getting drugs through the blood-brain barrier and the brain’s limited immune response to tumors. Nonetheless, the application of drugs that block cancer cell proteins used to evade attack by T cells, checkpoint inhibitors, is explored as immunotherapeutic approaches for glioblastoma. Despite the limited positive outcomes observed for checkpoint inhibitors to treat glioblastoma, the results of trials may help to identify important biomarkers that can be used to predict which patients could respond favorably to these immunotherapies.
Another immunotherapeutic strategy studied for its potential application in glioblastoma is chimeric antigen receptor (CAR)-T cell therapy. This personalized approach involves the use of a patient’s own immune system to fight cancer. A patient’s T cells are collected and modified at the molecular level to express receptors specific for the antigens of the patient’s tumor. These modified T cells are grown to a level needed to have adequate immune activity and injected into the patient. Once back in the body, these modified T cells can activate and attack cancer cells once they bind to the antigen.
The main CAR-T target studied is an epidermal growth factor receptor variant, EGFRvIII, which plays a crucial role in the pathogenesis of glioblastoma. Although results of clinical trials to date do not show direct effects on halting tumor growth or overall survival, they seem to enhance the brain’s immune response. Bi- and trispecific CAR-T cells (that can target 2 or 3 different antigens, respectively) have been developed, and human trials are underway to determine the effectiveness and safety of trispecific CAR-T cells that target glioblastoma antigens, namely human epidermal growth factor receptor 2, interleukin-13 receptor alpha-2, and ephrin type-A receptor.
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Can Immunotherapy Succeed in Glioblastoma?. (2018). National Cancer Institute. Retrieved 19 June 2018, from https://www.cancer.gov/news-events/cancer-currents-blog/2018/immunotherapy-glioblastoma