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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

基本信息

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
项目类别：
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

项目摘要

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.

胶质瘤是一种高度侵袭性的脑肿瘤，作为残留肿瘤不能完全切除肿瘤。细胞通常会渗入周围的功能性脑组织，并受到血脑屏障(BBB)的保护。血脑屏障是治疗药物有效输送到中枢神经系统的重要障碍。血脑屏障形成高度选择性的半透边界，防止循环血液中的溶质从进入到颅内环境中。因此，迫切需要新的药物输送方法。从血脑屏障到神经胶质瘤。为了解决这些未得到满足的主要医疗需求，我们建议在这里开发新的用于向胶质瘤输送刺激性激动剂的纳米颗粒。我们将开发可以调整的纳米粒子不同的靶向部分并有效地递送到胶质瘤；通过转化诱导抗肿瘤免疫反应从“冷”的胶质瘤转变为“热的”肿瘤；根除已建立的胶质瘤；并产生持续的抗胶质瘤豁免权。本补充申请侧重于将从家长R01拨款中获得的知识应用于靶向神经胶质瘤刺激剂，实现抗肿瘤免疫。因此，这代表着一个新的补充性研究部分，与赠款的原始目标直接相关并扩大范围它的翻译潜力和应用。