Developing Novel Therapeutic Approaches Targeting Macrophages in GBM

开发针对 GBM 巨噬细胞的新型治疗方法

• 批准号: 10815321
• 负责人: Y. Alan Wang
• 金额: $ 35.53万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10815321
• 关键词: Developing; Novel; Therapeutic; Approaches; Targeting

Project Summary GBM remains the most lethal brain cancer with no effective therapeutics. It has been shown that the majority of stromal cells in GBM are tumor-associated macrophages (TAMs), which contribute to tumor microenvironment heterogeneity and promote GBM progression. We have recently defined molecular pathways leading to macrophage recruitment and polarization. Our preliminary data showed that PTEN mutation/deletion in GBM triggers immune response by enhancing macrophage recruitment through LOX. In addition, we have also identified TBK1 as a key signaling node regulating macrophage polarization. Aim 1: we will elucidate the mechanism of LOX mediated macrophage recruitment in GBM; Aim 2: we will determine the molecular basis of TBK1 mediated macrophage polarization in GBM; Aim 3: we will perform preclinical trials targeting LOX and TBK1 in combination with standard of care and immune checkpoint blockade to develop novel therapeutic approach for GBM patients.

项目摘要 GBM仍然是最致命的脑癌，没有有效的疗法。已经表明 GBM中的大多数基质细胞是肿瘤相关的巨噬细胞（TAM），有助于 肿瘤微环境异质性并促进GBM进展。我们最近有 定义的分子途径导致巨噬细胞募集和极化。我们的初步 数据表明，GBM中的PTEN突变/缺失通过增强来触发免疫反应 通过LOX募集巨噬细胞。此外，我们还将TBK1确定为钥匙 信号传导节点调节巨噬细胞极化。目标1：我们将阐明 LOX介导的GBM中的巨噬细胞募集；目标2：我们将确定的分子基础 TBK1介导的GBM中的巨噬细胞极化；目标3：我们将执行临床前试验的目标 LOX和TBK1与护理标准和免疫检查点结合使用以发展 GBM患者的新型治疗方法。