Core C Mouse Model Core

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Project Summary The long-range objectives of the Core are to utilize pertinent mouse models of Glioblastoma Multiforme (GBM) to study the roles of Extracellular Vesicles (EVs) in influencing the tumor microenvironment and therapeutic responses to standard of care (SoC) treatment, gene mediated cytotoxic immunotherapy (GMCI) and immune checkpoint inhibitors therapies. The goals of the Core are to provide technical, intellectual and scientific support to all three Projects of this P01 application. The Core has been providing valuable services to this PPG for the last 4 years and will continue to be a central component of the overall goals of the Program by delivering an appropriate platform to conduct pre-clinical studies that will educate and expedite clinical trials. We will utilize validated EGFR- and PDGFRα-based GBM GEM models and well-characterized PDX models and their Glioma Stem Cells (GSCs) to address the needs of the Projects. Animal transfer protocols between the different institutions are in place. We will adapt and refine these models to meet the evolving requirements of each individual Project, including the generation and characterization of new strains of mice for the detection of fluorescently tagged microglial cells. The Core is perfectly positioned to bring technology and knowhow to bear on the science of this P01. The Specific Aims are: Aim 1) To evaluate and implement GMCI therapy in the context of standard of care treatments in EGFR- and PDGFRα-based GEM and PDX models. Aim 2) To utilize EGFR- and PDGFRα-based pre-clinical GEM models to evaluate the functions of EVs in modulating immune checkpoint inhibitors immunotherapy. Aim 3) To design, generate and characterize genetically engineered transgenic strains of mice with fluorescently labeled microglia for the study of GBM tumor-derived EV on microglial function.