Core C Mouse Model Core

项目摘要 核心的长期目标是利用相关的多形性胶质母细胞瘤小鼠模型 (GBM)研究细胞外囊泡（EVs）在影响肿瘤微环境中的作用， 对标准治疗（SoC）的治疗反应，基因介导的细胞毒性免疫治疗（GMCI） 和免疫检查点抑制剂疗法。核心的目标是提供技术，智力和 为本P01申请的所有三个项目提供科学支持。核心一直在提供宝贵的服务， 在过去的4年里，这一PPG将继续成为该计划总体目标的核心组成部分， 提供一个适当的平台来进行临床前研究，这将教育和加快临床试验。 我们将利用经验证的基于EGFR和PDGFRα的GBM GEM模型和充分表征的PDX模型 及其神经胶质瘤干细胞（GSC），以满足项目的需求。之间的动物转移方案 不同的机构已经到位。我们将调整和完善这些模型，以满足不断变化的需求 每个单独项目，包括用于检测的新小鼠品系的产生和表征 荧光标记的小胶质细胞。核心是完美的定位，使技术和诀窍， 对这件事的科学性有影响具体目的是：目的1）评估和实施GMCI治疗在 基于EGFR和PDGFRα的GEM和PDX模型中的标准治疗背景。目标2）利用 基于EGFR和PDGFRα的临床前GEM模型，用于评价EV在调节免疫中的功能 检查点抑制剂免疫疗法。目的3）设计、产生和表征基因工程 用荧光标记的小胶质细胞研究GBM肿瘤衍生的EV的转基因小鼠品系， 小胶质细胞功能

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.