The role of reactive gliosis in response to Immunotherapy in Diffuse Midline Glioma
Diffuse midline glioma (DMG) is a universally fatal childhood brain malignancy with no sufficient treatment options. With brain cancer emerging as the leading cause of cancer-related death in children and young adults, new treatments are desperately needed. Our research program has developed a new treatment called RNA nanoparticle vaccines (RNA-NPs) to treat DMG and other cancers. RNA-NPs are a personalized immunotherapy treatment that activates the body’s own immune system to recognize and kill cancer cells. In preclinical trials, RNA-NPs have shown strong evidence for anti-cancer activity, resulting in long-term and even curative outcomes. Since RNA-NP treatment works by activating the immune system, it can produce changes in MRI imaging that can be mistaken for tumor progression. Currently we do not understand why these changes in imaging occur. We also do not have any reliable methods for distinguishing the difference between treatment activity and treatment failure (i.e. tumor progression). The goal of this research proposal is to improve our understanding of how RNA-NPs work, as well as identify new methods to monitor treatment response via imaging.
Project Goal:
In this grant proposal, we include a series of experiments with three main goals. First, to understand origin and function of cells in the brain, both immune and neural, that work together to kill DMG cells. Second, we will test a number of advanced imaging methods together with biomarker and metabolic screening to help us determine whether RNA-NP treatment is working, or if a tumor has relapsed. Third, and most importantly, the results of this study will help us to identify strategic methods to minimize side effects without reducing the effectiveness of treatment.
