Novel focused ultrasound enhanced calreticulin-nanoparticle for immune primed melanoma immunotherapy

用于免疫引发黑色素瘤免疫治疗的新型聚焦超声增强钙网蛋白纳米颗粒

基本信息

  • 批准号:
    10177969
  • 负责人:
  • 金额:
    $ 32.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-06-04 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Summary Malignant melanoma in advanced stages is a highly lethal form of cancer, refractory to chemo- and radio-therapy, and the median survival is typically less than 4years. To improve response rates, antibodies that target CTL-4, PD1, and PDL1 has gained prominence, and can achieve a response rate of ~50% in metastatic cases. This is promising but a large proportion of patients still do not respond to immune therapies due to the absence of infiltrating T-cells, and presence of aberrant and suppresive signaling pathways that blunt the expression of checkpoint proteins (e.g. CD47, PDL1). To promote inflamed melanoma microenvironment, recent studies indicate that image-guided focused ultrasound (FUS) can i) mediate precise mechanical perturbation and elevation of tumor temperature to induce tumor antigen release and ii) upregulate calreticulin (CRT), a protein that is key to the activation of local and systemic anti-immunity. However, the exact mechanisms and how to translate this approach for clinical treatment of malignant melanoma is poorly understood. The goal of this project is to combine ultrasound guided FUS with novel CRT-NP, a liposome-plasmid nanoparticle agent that transfects melanoma cells to induce expression of CRT. Our in vitro and in vivo data in murine melanoma suggest that combined local treatment with CRT-NP/FUS (CFUS) enhances expression of CRT and modulates innate (CD47) and adaptive checkpoint proteins (PDL1); all of which significantly enhance the local and systemic immune priming and anti-tumor responses. Based on this premise, our central hypothesis is that CFUS targeted optimization of the CRT/CD47/PDL1 axis will provide powerful immune priming and generation of systemic immunity against malignant melanoma. To test our hypothesis, we will mechanistically dissect and understand CFUS-mediated immune priming in a B16 orthotopic and genetically-engineered mouse melanoma model (Aim 1 & 2) and translate this approach to clinical use in trials using client-owned dogs with spontaneous oral melanoma (Aims 3). Specifically, we will evaluate the impact of the CFUS treatment sequence, FUS exposures, and CRT-activation mechanisms in murine melanoma and translate this information to improve efficacy of checkpoint blockage in murine and canine tumor models. We expect that the successful optimization of local CFUS in this project will liberate tumors from their immune- suppressive state, achieve consistent and predictable clonal expansion of cytotoxic immune cells, and improve immunotherapy efficacy independent of cancer complexity. If successful, this method will provide a promising new avenue for treating melanoma and other types of solid tumor (e.g., breast, prostate) by significantly overcoming current immunotherapy barriers.
总结

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 }}

Ashish Ranjan其他文献

Ashish Ranjan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('Ashish Ranjan', 18)}}的其他基金

Role of histotripsy synergized CD40 signaling in the re-engineering of cold tumors
组织解剖协同 CD40 信号传导在冷肿瘤再造中的作用
  • 批准号:
    10390557
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
Novel focused ultrasound enhanced calreticulin-nanoparticle for immune primed melanoma immunotherapy
用于免疫引发黑色素瘤免疫治疗的新型聚焦超声增强钙网蛋白纳米颗粒
  • 批准号:
    10627822
  • 财政年份:
    2019
  • 资助金额:
    $ 32.96万
  • 项目类别:
Novel focused ultrasound enhanced calreticulin-nanoparticle for immune primed melanoma immunotherapy
用于免疫引发黑色素瘤免疫治疗的新型聚焦超声增强钙网蛋白纳米颗粒
  • 批准号:
    10434835
  • 财政年份:
    2019
  • 资助金额:
    $ 32.96万
  • 项目类别:
Image-guided tumor drug delivery by ultrasound-detected heat-released liposome
通过超声检测的热释放脂质体进行图像引导的肿瘤药物递送
  • 批准号:
    8773087
  • 财政年份:
    2014
  • 资助金额:
    $ 32.96万
  • 项目类别:

相似海外基金

Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
  • 批准号:
    10591918
  • 财政年份:
    2023
  • 资助金额:
    $ 32.96万
  • 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
  • 批准号:
    23K15383
  • 财政年份:
    2023
  • 资助金额:
    $ 32.96万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
  • 批准号:
    23H03556
  • 财政年份:
    2023
  • 资助金额:
    $ 32.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
  • 批准号:
    23K17212
  • 财政年份:
    2023
  • 资助金额:
    $ 32.96万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
  • 批准号:
    22H03519
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
  • 批准号:
    563657-2021
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
    Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
  • 批准号:
    10521849
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
  • 批准号:
    10671022
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
  • 批准号:
    10670918
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
Adverse Effects of Using Laser Diagnostics in High-Speed Compressible Flows
在高速可压缩流中使用激光诊断的不利影响
  • 批准号:
    RGPIN-2018-04753
  • 财政年份:
    2022
  • 资助金额:
    $ 32.96万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了