ImmunoPET Assessment of anti-CD47 Immunotherapy Delivery to Glioblastoma with Focused Ultrasound

使用聚焦超声对胶质母细胞瘤进行抗 CD47 免疫治疗的免疫PET评估

基本信息

  • 批准号:
    10041000
  • 负责人:
  • 金额:
    $ 42.01万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Gliomas are the most common malignant human brain tumors, accounting for the majority of deaths from primary brain neoplasms. Even when treated with surgery, radiotherapy, and chemotherapy, patients with grade IV glioblastoma (GB) have a life expectancy of only 14 months. A major challenge to treating GB is its highly invasive nature, as infiltrating cancer cells are “protected” from exposure to systemically administered chemo- and immunotherapies by the blood brain barrier (BBB). To overcome this physical this barrier to drug delivery, we non-invasively open the BBB via the activation of intravascular microbubbles (MBs) with MRI-guided focused ultrasound (FUS). In this proposal, we will utilize this non-invasive approach to deliver anti-CD47 immunotherapy (mCD47) to gliomas. CD47, a surface molecule expressed by cancer cells that sends a so-called “don’t eat me” signal to phagocytic cells, has garnered considerable attention recently because functionally blocking CD47 elicits control of many neoplasms, including primary brain tumors. Our proposal has 2 specific aims. In Aim 1, we will determine, through the use of 89Zr-ImmunoPET imaging, how the timing and sequencing of FUS application with respect to drug administration affects mCD47 delivery to GL261 gliomas. BBB opening with FUS and MBs is extremely complex, with several factors potentially influencing mAb delivery (e.g. time-varying modulation of tumor interstitial pressure, active vs. passive transport, and altered efflux transporter expression levels). Thus, there is strong rationale to definitively establish how the timing and sequencing of FUS with respect to drug administration affects the delivery of mCD47. Next, Aim 2 will investigate the experimental therapeutic efficacy of mCD47 against gliomas when delivered using the most effective timing and sequencing regimen identified in Aim 1. We will evaluate the ability of FUS to improve mCD47 efficacy in controlling GL261 tumor growth, blocking infiltration, and improving survival. Reproducibility will be tested using the CT-2A glioma model, which is also both highly infiltrative and responsive to mCD47. By mid-2019, dozens of patients worldwide had been treated with FUS and MBs to elicit BBB opening, thus a clear precedent has been set for translation of this technology. UVa houses a low-frequency clinical MR image-guided FUS system (Insightec Exablate Neuro) that is specialized for this application, and we are preparing for our first clinical trial for drug delivery across the BBB in GB patients using FUS and MBs. Thus, if we are able to demonstrate therapeutic efficacy of mCD47 in combination with FUS and MBs, we are exceptionally well-positioned to rapidly translate these findings to the clinic.
胶质瘤是人类最常见的恶性脑肿瘤,占死亡人数的大部分

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Magnetic Resonance Imaging of Mouse Cerebral Cavernomas Reveal Differential Lesion Progression and Variable Permeability to Gadolinium.
小鼠脑海绵状血管瘤的磁共振成像揭示了不同的病变进展和对钆的可变渗透性。
  • DOI:
    10.1161/atvbaha.122.318938
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Fisher,DelaneyG;Sharifi,KhadijehA;Ulutas,EZeynep;Kumar,JeyanS;Kalani,MYasharS;Miller,GWilson;Price,RichardJ;Tvrdik,Petr
  • 通讯作者:
    Tvrdik,Petr
Computational model of brain endothelial cell signaling pathways predicts therapeutic targets for cerebral pathologies.
Applications of focused ultrasound-mediated blood-brain barrier opening.
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Richard J. Price其他文献

A novel ‘bottom-up’ synthesis of few- and multi-layer graphene platelets with partial oxidation via cavitation
  • DOI:
    10.1016/j.ultsonch.2019.03.020
  • 发表时间:
    2019-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    Richard J. Price;Paul I. Ladislaus;Graham C. Smith;Trevor J. Davies
  • 通讯作者:
    Trevor J. Davies
Dynamics of Adult Axin2 Cell Lineage Integration in Granule Neurons of the Dentate Gyrus
齿状回颗粒神经元中成人 Axin2 细胞谱系整合的动态
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Khadijeh A. Sharifi;Faraz Farzad;Sauson Soldozy;Richard J. Price;M. Y. S. Kalani;P. Tvrdik
  • 通讯作者:
    P. Tvrdik
Focused ultrasound augments the delivery and penetration of model therapeutics into cerebral cavernous malformations
聚焦超声增强了模型治疗药物向脑海绵状血管畸形的递送和渗透。
  • DOI:
    10.1016/j.jconrel.2025.113861
  • 发表时间:
    2025-07-10
  • 期刊:
  • 影响因子:
    11.500
  • 作者:
    Delaney G. Fisher;Matthew R. Hoch;Catherine M. Gorick;Claire Huchthausen;Victoria R. Breza;Khadijeh A. Sharifi;Petr Tvrdik;G. Wilson Miller;Richard J. Price
  • 通讯作者:
    Richard J. Price
Focused ultrasound-microbubble treatment arrests the growth and formation of cerebral cavernous malformations
聚焦超声微泡治疗可阻止脑海绵状畸形的生长和形成
  • DOI:
    10.1038/s41551-025-01390-z
  • 发表时间:
    2025-05-13
  • 期刊:
  • 影响因子:
    26.600
  • 作者:
    Delaney G. Fisher;Tanya Cruz;Matthew R. Hoch;Khadijeh A. Sharifi;Ishaan M. Shah;Catherine M. Gorick;Victoria R. Breza;Anna C. Debski;Joshua D. Samuels;Jason P. Sheehan;David Schlesinger;David Moore;James W. Mandell;John R. Lukens;G. Wilson Miller;Petr Tvrdik;Richard J. Price
  • 通讯作者:
    Richard J. Price

Richard J. Price的其他文献

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{{ truncateString('Richard J. Price', 18)}}的其他基金

Genome Editing the Blood-Brain Barrier with Sonoselective Focused Ultrasound
利用声选择性聚焦超声对血脑屏障进行基因组编辑
  • 批准号:
    10403487
  • 财政年份:
    2021
  • 资助金额:
    $ 42.01万
  • 项目类别:
Genome Editing the Blood-Brain Barrier with Sonoselective Focused Ultrasound
利用声选择性聚焦超声对血脑屏障进行基因组编辑
  • 批准号:
    10554403
  • 财政年份:
    2021
  • 资助金额:
    $ 42.01万
  • 项目类别:
Innovative systemic gene therapy for treating Parkinson's disease
治疗帕金森病的创新系统基因疗法
  • 批准号:
    10164880
  • 财政年份:
    2019
  • 资助金额:
    $ 42.01万
  • 项目类别:
Innovative systemic gene therapy for treating Parkinson's disease
治疗帕金森病的创新系统基因疗法
  • 批准号:
    9927696
  • 财政年份:
    2019
  • 资助金额:
    $ 42.01万
  • 项目类别:
Innovative systemic gene therapy for treating Parkinson's disease
治疗帕金森病的创新系统基因疗法
  • 批准号:
    10394379
  • 财政年份:
    2019
  • 资助金额:
    $ 42.01万
  • 项目类别:
Innovative systemic gene therapy for treating Parkinson's disease
治疗帕金森病的创新系统基因疗法
  • 批准号:
    10609832
  • 财政年份:
    2019
  • 资助金额:
    $ 42.01万
  • 项目类别:
Endothelial DNA Methylation, Arteriogenic Capacity, and Shear Stress "Set-Point."
内皮 DNA 甲基化、动脉生成能力和剪切应力“设定点”。
  • 批准号:
    9311466
  • 财政年份:
    2017
  • 资助金额:
    $ 42.01万
  • 项目类别:
Application of Laser Speckle Flowmetry to Vascular Remodeling
激光散斑流量计在血管重塑中的应用
  • 批准号:
    8765491
  • 财政年份:
    2014
  • 资助金额:
    $ 42.01万
  • 项目类别:
Application of Laser Speckle Flowmetry to Vascular Remodeling
激光散斑流量计在血管重塑中的应用
  • 批准号:
    8887112
  • 财政年份:
    2014
  • 资助金额:
    $ 42.01万
  • 项目类别:
Bevacizumab Delivery to Glioblastoma with MR-Guided Focused Ultrasound
通过 MR 引导聚焦超声将贝伐珠单抗递送至胶质母细胞瘤
  • 批准号:
    8628120
  • 财政年份:
    2013
  • 资助金额:
    $ 42.01万
  • 项目类别:

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揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
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