Vaccine-based immunotherapy for glioblastoma using tumor cells, Zika virus, and a checkpoint inhibitor
2020
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Vaccine-based immunotherapy for glioblastoma using tumor cells, Zika virus, and a checkpoint inhibitor
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2020
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Glioblastoma multiforme (GBM), the most common malignant brain tumor, is very aggressive with a survival rate of less than 5% at five years, despite the current treatment regimen comprised of surgical resection, radiation therapy, and chemotherapy with temozolomide. New and more effective cancer treatments may stem from immunotherapies, which amplify and modify the immune response to target tumor cells. These immunotherapies include checkpoint inhibitors, vaccines, and oncolytic viruses. When used as standalone treatments for GBM, they moderately promote survival and remission. However, combinations of immunotherapies may act synergistically. This project aims to generate a more effective treatment for GBM that employs dual immunotherapies: a checkpoint inhibitor and a cancer vaccine. In a GL261 mouse model of malignant gliomas, we found that this combination yields an overall survival of 75%, compared to a survival rate of 25% with the vaccine alone. Our results suggest that the additional checkpoint inhibitor attenuates tumor-driven immunosuppression and improves survival without apparent toxic effects. While this may encourage the addition of more immunotherapies into a single treatment for GBM, closer evaluation of chemotoxicity is necessary before a finalized treatment is viable for clinical trials. Nonetheless, our findings demonstrate the promising efficacy of combining immunotherapies.
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This research was supported by the Undergraduate Research Opportunities Program (UROP).
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Guo, Winston L.; Chrostek, Matthew R.; Toman, Nikolas G.; Tran, Sarah K.; Crane, Andrew T.; Low, Walter C.. (2020). Vaccine-based immunotherapy for glioblastoma using tumor cells, Zika virus, and a checkpoint inhibitor. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/212373.
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