Next Gen Virotherapy for GBM

GBM 的下一代病毒疗法

基本信息

  • 批准号:
    10818683
  • 负责人:
  • 金额:
    $ 52.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

Abstract: The overall goal of this application is to develop a NOTCH blocking strategy in combination with oHSV that can be safely delivered to intracranial GBM to enhance therapeutic efficacy without neurologic toxicity. In the normal brain, Notch signaling plays a significant role in memory processing and adult neurogenesis. In glioblastoma (GBM) NOTCH signaling has also been implicated in the development of resistance to chemotherapy and radiation, and contributes to the dismal survival associated with GBM, a disease associated with a less than 2 year median survival despite treatment with surgery, radiation, temozolomide, and with tumor treating field device. The overall goal of this application is to understand the impact of specific NOTCH ligand mediated NOTCH activation on oHSV therapy for brain tumors. Since NOTCH signaling plays a significant role in the brain in memory processing and adult neurogenesis, we will also evaluate the impact of blocking specific ligands on memory development and safety for intracranial usage. In our preliminary results we have identified that oHSV infection induces NOTCH activation in tumor and tumor associated macrophages (TAM). NOTCH activation of TAMs results in induction of CCL2 that recruits monocytic MDSCs to infected tumors. While oHSV treatment awakens anti-tumor efficacy, these monocytic MDSCs limit the immunotherapeutic benefit by educating an immune-suppressive environment in tumors. It has been shown that different NOTCH ligands have different effects on anti-tumor immunity. For example, DLL1-mediated NOTCH activation is important for T cell maturation into memory cells and its overexpression augments T cell activity and anti-tumor immunity. While JAG1, and to a lesser extent JAG2, induce PD-1 and suppress T cell immunity. Thus, we hypothesize that blockade of JAG1 mediated signaling should enhance virotherapy induced anti-tumor immunity, and its transient expression by an oHSV would not create a neurologic memory deficit in mice. Since, membrane bound ligands can activate NOTCH signaling and soluble monomeric ligands can inhibit NOTCH signaling, here we will test the effect of blocking individual NOTCH ligand mediated NOTCH activation on oHSV efficacy and anti-tumor immunity (Aim 1). In aim 2 we will create an oHSV that can effectively block virus induced ligand specific NOTCH signaling to augment virus induced anti-tumor immunity. This virus will also be evaluated for safety, sensitivity to ACV, and effect on mouse behavior and memory. Further we have found that combination of an oHSV with irradiation synergistically activates NOTCH signaling. In aim 3 we will evaluate the effect of this virus in combination with irradiation.
文摘:

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Balveen Kaur其他文献

Balveen Kaur的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Balveen Kaur', 18)}}的其他基金

Next Gen Virotherapy for GBM
GBM 的下一代病毒疗法
  • 批准号:
    10467244
  • 财政年份:
    2022
  • 资助金额:
    $ 52.96万
  • 项目类别:
Optimizing oncolytic virus therapy for glioblastoma
优化胶质母细胞瘤的溶瘤病毒治疗
  • 批准号:
    9807942
  • 财政年份:
    2019
  • 资助金额:
    $ 52.96万
  • 项目类别:
Optimizing oncolytic virus therapy for glioblastoma
优化胶质母细胞瘤的溶瘤病毒治疗
  • 批准号:
    10618742
  • 财政年份:
    2019
  • 资助金额:
    $ 52.96万
  • 项目类别:
Enhancing viral oncolysis with vasculostatin gene delivery
通过血管抑素基因传递增强病毒溶瘤作用
  • 批准号:
    9900732
  • 财政年份:
    2017
  • 资助金额:
    $ 52.96万
  • 项目类别:
Project 3: Circumventing extracellular Adenosine barrier to oncolytic virotherapy
项目3:绕过溶瘤病毒疗法的细胞外腺苷屏障
  • 批准号:
    10712282
  • 财政年份:
    2013
  • 资助金额:
    $ 52.96万
  • 项目类别:
Project 3: Notch signaling in oHSV therapy for GBM
项目 3:oHSV 治疗 GBM 中的 Notch 信号传导
  • 批准号:
    10491211
  • 财政年份:
    2013
  • 资助金额:
    $ 52.96万
  • 项目类别:
Project 3: Notch signaling in oHSV therapy for GBM
项目 3:oHSV 治疗 GBM 中的 Notch 信号传导
  • 批准号:
    10019365
  • 财政年份:
    2013
  • 资助金额:
    $ 52.96万
  • 项目类别:
Project 3: Notch signaling in oHSV therapy for GBM
项目 3:oHSV 治疗 GBM 中的 Notch 信号传导
  • 批准号:
    10251084
  • 财政年份:
    2013
  • 资助金额:
    $ 52.96万
  • 项目类别:
Enhancing Viral Oncolysis with Vasculostatin Gene Delivery
通过血管抑素基因传递增强病毒溶瘤作用
  • 批准号:
    8638899
  • 财政年份:
    2011
  • 资助金额:
    $ 52.96万
  • 项目类别:
Enhancing Viral Oncolysis with Vasculostatin Gene Delivery
通过血管抑素基因传递增强病毒溶瘤作用
  • 批准号:
    8450666
  • 财政年份:
    2011
  • 资助金额:
    $ 52.96万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 52.96万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了