Novel nano-vaccine technology for inducing immunity against gliomas

用于诱导神经胶质瘤免疫力的新型纳米疫苗技术

基本信息

  • 批准号:
    10443896
  • 负责人:
  • 金额:
    $ 50.19万
  • 依托单位:
  • 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

Abstract Despite the success of immune checkpoint blockade in cancer therapy, their use has benefited only a subset of cancer patients. The multiple mechanisms utilized by tumors to inhibit an anti-tumor immune response have impeded their widespread use as monotherapies, and this is particularly true for gliomas. Therefore, there exists a critical need for new, complementary strategies for achieving powerful and durable immune responses against gliomas. In particular, mutant isocitrate-dehydrogenase-1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. We have developed a fully immune competent murine mIDH1 model by incorporating genetic lesions encountered in the human disease into the genomic DNA of neural progenitor cells using Sleeping Beauty Transposase and shown that these intracranial tumors exhibit the hallmarks of human mIDH1 glioma. Our long- term research goal is to develop novel strategies that can achieve immune stimulation with potent anti-mIDH1 glioma immunity. Our main objectives in this application are to engineer a powerful and safe platform vaccine technology for inducing robust, durable anti-tumor memory T-cell responses against mIDH1 gliomas. To this end, we have developed a new vaccine technology based on synthetic high-density lipoprotein (sHDL) nanodiscs. We have shown that sHDL nanodiscs efficiently deliver antigens and adjuvant molecules to antigen- presenting cells and achieve strong T-cell responses with robust cytotoxic potential. Here, we propose to evaluate the therapeutic efficacy of sHDL nanoparticles in genetically engineered murine glioma models and transplantable intracranial gliomas. Specifically, we propose to (1) optimize our nanotechnology for improved mIDH1 Ag delivery and elicit durable memory T-cell responses against mIDH1 glioma (Aim 1); (2) evaluate their efficacy to eradicate mIDH1 gliomas using neurospheres derived from the mIDH1 genetically engineered glioma model (GEM) implanted into immunocompetent mice (Aim 2); (3) test the hypothesis that combining nanodisc vaccination with standard of care (radiation) and anti-PD-L1 immune checkpoint blockade will elicit robust anti- mIDH1 glioma immunity with long-term immunological memory in mIDH1 GEMs. These studies will shed new light on nano-vaccine delivery platforms for precision immunotherapy. More broadly, the work proposed will address current technical limitations in vaccine technologies and potentially lead to a new treatment option for mIDH1 glioma patients.
摘要

项目成果

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Maria G Castro其他文献

Maria G Castro的其他文献

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{{ truncateString('Maria G Castro', 18)}}的其他基金

Systemic Delivery of Targeted Bi-Compartmental Nanoparticles for Glioblastoma Therapeutics
用于胶质母细胞瘤治疗的靶向双室纳米颗粒的系统递送
  • 批准号:
    10584553
  • 财政年份:
    2022
  • 资助金额:
    $ 50.19万
  • 项目类别:
Uncover the role of H3.3-G343R mutation in shaping the DNA damage response, anti-tumor immunity and mechanisms of resistance in glioma.
揭示 H3.3-G343R 突变在塑造神经胶质瘤 DNA 损伤反应、抗肿瘤免疫和耐药机制中的作用。
  • 批准号:
    10384185
  • 财政年份:
    2022
  • 资助金额:
    $ 50.19万
  • 项目类别:
Uncover the role of H3.3-G343R mutation in shaping the DNA damage response, anti-tumor immunity and mechanisms of resistance in glioma.
揭示 H3.3-G343R 突变在塑造神经胶质瘤 DNA 损伤反应、抗肿瘤免疫和耐药机制中的作用。
  • 批准号:
    10550245
  • 财政年份:
    2022
  • 资助金额:
    $ 50.19万
  • 项目类别:
Systemic Delivery of Targeted Bi-Compartmental Nanoparticles for Glioblastoma Therapeutics
用于胶质母细胞瘤治疗的靶向双室纳米颗粒的系统递送
  • 批准号:
    10462033
  • 财政年份:
    2022
  • 资助金额:
    $ 50.19万
  • 项目类别:
Novel nano-vaccine technology for inducing immunity against gliomas
用于诱导神经胶质瘤免疫力的新型纳米疫苗技术
  • 批准号:
    10655464
  • 财政年份:
    2021
  • 资助金额:
    $ 50.19万
  • 项目类别:
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
  • 财政年份:
    2021
  • 资助金额:
    $ 50.19万
  • 项目类别:
Chemo-immunotherapy strategy for pediatric high grade glioma
儿童高级别胶质瘤的化学免疫治疗策略
  • 批准号:
    10296214
  • 财政年份:
    2021
  • 资助金额:
    $ 50.19万
  • 项目类别:
Novel nano-vaccine technology for inducing immunity against gliomas
用于诱导神经胶质瘤免疫力的新型纳米疫苗技术
  • 批准号:
    10877283
  • 财政年份:
    2021
  • 资助金额:
    $ 50.19万
  • 项目类别:
Novel nano-vaccine technology for inducing immunity against gliomas
用于诱导神经胶质瘤免疫力的新型纳米疫苗技术
  • 批准号:
    10241830
  • 财政年份:
    2021
  • 资助金额:
    $ 50.19万
  • 项目类别:
Immune-suppressive Myeloid Cells in the Glioma Microenvironment: Signaling Mechanisms and Novel Therapeutic Strategies
胶质瘤微环境中的免疫抑制骨髓细胞:信号传导机制和新的治疗策略
  • 批准号:
    9304356
  • 财政年份:
    2015
  • 资助金额:
    $ 50.19万
  • 项目类别:

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  • 财政年份:
    2001
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