Administrative Diversity Supplement- Novel Nano-Vaccine Technology for Inducing Immunity Against Gliomas

行政多样性补充-诱导神经胶质瘤免疫的新型纳米疫苗技术

• 批准号: 10622660
• 负责人: Maria G Castro
• 金额: $ 8.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622660
• 关键词: Address; Biocompatible Materials; Biology; Blood; Blood - brain barrier anatomy; Brain Neoplasms; Drug Delivery Systems; Engineering; Environment; Excision; Glioma; Goals; Grant; Immune response; Immunity; Knowledge; Lead; Medical; Neuraxis; Parents; Public Health; Research; Residual Tumors; STING agonists; Technology; Therapeutic Agents; Tumor Immunity; anti-tumor immune response; brain tissue; cancer immunotherapy; design; improved; nanoparticle; nanoparticle delivery; nanovaccine; neoplastic cell; novel; novel strategies; prevent; solute; translational applications; translational potential; tumor

Gliomas are highly aggressive brain tumors and complete tumor resection is not achievable as residual tumor cells routinely infiltrate the surrounding functional brain tissue and are protected by the blood brain barrier (BBB). The BBB presents a significant obstacle for effective delivery of therapeutic agents to the central nervous system. The BBB forms a highly selective semipermeable border that prevents solutes in the circulating blood from crossing into the intracranial environment. Thus, there is an urgent need for new approaches for drug delivery through the BBB to gliomas. To address these major unmet medical needs, here we propose to develop new nanoparticles for delivering STING agonist to gliomas. We will develop nanoparticles that can be tuned with different targeting moieties and effectively delivered to gliomas; elicit anti-tumor immune response by converting the “cold” glioma tumors to “hot” tumors; eradicate established gliomas; and generate sustained anti-gliomas immunity. This Supplement application focuses on applying the knowledge gained from the parent R01 grant to target STING agonists to gliomas and achieve anti-tumor immunity against gliomas. Therefore, this represents a new and complementary research component that directly relates to original goals of the grant and broadens its translational potential and application.

胶质瘤是高度侵袭性的脑肿瘤，由于残留肿瘤， 细胞通常渗入周围的功能性脑组织，并受到血脑屏障（BBB）的保护。 BBB对治疗剂有效递送至中枢神经系统存在显著障碍。 血脑屏障形成一个高度选择性的半透性边界，阻止循环血液中的溶质 进入颅内环境因此，迫切需要用于药物递送的新方法 通过血脑屏障转移到神经胶质瘤为了解决这些主要的未满足的医疗需求，我们建议开发新的 用于将STING激动剂递送至神经胶质瘤的纳米颗粒。我们将开发纳米粒子， 不同的靶向部分，并有效地递送到胶质瘤;通过转化引发抗肿瘤免疫应答 将“冷”胶质瘤肿瘤转化为“热”肿瘤;根除已建立的胶质瘤;并产生持续的抗胶质瘤 免疫力本补充申请的重点是将从父R 01补助金中获得的知识应用于 将STING激动剂靶向神经胶质瘤并实现针对神经胶质瘤的抗肿瘤免疫。因此，这代表着 一个新的和互补的研究组成部分，直接关系到赠款的原始目标，并扩大 其翻译潜力和应用。