Project 2

项目2

基本信息

  • 批准号:
    10270394
  • 负责人:
  • 金额:
    $ 55.4万
  • 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:
    2021-09-16 至 2026-07-31
  • 项目状态:
    未结题

项目摘要

Pancreatic ductal adenocarcinoma is an extremely lethal disease with the lowest 1-year and 5-year survival rates of any cancer. This is due, in part, to the extremely metastatic behavior of pancreas carcinoma cells and their extreme resistance to both chemical and radiotherapies. Importantly, we now know that a strong, but nevertheless unique, fibrotic and immunosuppressive stromal response is present in PDA. This intense fibroinflammatory, or desmoplastic, response is essentially pathognomonic for PDA and limits infiltration of anti-tumor immune cells and also their ability to move throughout and sample the tumor volume. Indeed, immunotherapies with immune checkpoint blockade or infusion of genetically modified cells are producing remarkable clinical responses in other advanced malignancies, but to date, success has been much more limited in PDA. However, focused preclinical strategies to disrupt the stroma or specifically engineer T cell therapies have shown promise in PDA. Thus, understanding the molecular basis for engineered T cell infiltration and identifying strategies to further enhance their infiltration, migration throughout tumor masses, and persistence and function in cancer will inform cell engineering strategies for improved treatment. Here, we test a number of focused hypotheses using integrated experiments, advanced imaging, and mathematical modeling to elucidate engineered T cell migratory mechanisms both in vivo and in engineered platforms in vitro and utilize genome editing and overexpression to engineer T cells that can maximally infiltrate and move throughout complex tumor microenvironments. We hypothesize that by enhancing the ability of engineered T cells to move throughout tumor we can profoundly improve their efficacy and employ combinations of stroma targeting and T cell therapies to improve disease outcomes. We will dissect mechanisms governing infiltration, longevity and functionality of engineered T cells and determine how engineered T cell migrate within the physically complex tumor environments. This information will be used engineer T cells that most effectively move throughout the entire tumor mass. Using these cells, we will perform rigorous preclinical evaluation of our engineered T cell approach in concert with rational stroma re-engineering. Our goals are aligned with Projects 1 and 3 where we seek to collectively elucidate fundamental mechanisms of immune cell migration and to innovate novel cell engineering approaches to eradicate cancer.
胰腺导管腺癌是一种极具致命性的疾病,其1年和5年生存率最低

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)

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Paolo Provenzano其他文献

Paolo Provenzano的其他文献

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{{ truncateString('Paolo Provenzano', 18)}}的其他基金

Research Testbed 1
研究试验台1
  • 批准号:
    10538593
  • 财政年份:
    2021
  • 资助金额:
    $ 55.4万
  • 项目类别:
Research Testbed 1
研究试验台1
  • 批准号:
    10374453
  • 财政年份:
    2021
  • 资助金额:
    $ 55.4万
  • 项目类别:
Project 2
项目2
  • 批准号:
    10700937
  • 财政年份:
    2021
  • 资助金额:
    $ 55.4万
  • 项目类别:
A platform to functionally sort and analyze tumor cells within combinatorial metastatic micorenvironments
在组合转移微环境中对肿瘤细胞进行功能分类和分析的平台
  • 批准号:
    10632016
  • 财政年份:
    2020
  • 资助金额:
    $ 55.4万
  • 项目类别:
A platform to functionally sort and analyze tumor cells within combinatorial metastatic micorenvironments
在组合转移微环境中对肿瘤细胞进行功能分类和分析的平台
  • 批准号:
    10161754
  • 财政年份:
    2020
  • 资助金额:
    $ 55.4万
  • 项目类别:
A platform to functionally sort and analyze tumor cells within combinatorial metastatic micorenvironments
在组合转移微环境中对肿瘤细胞进行功能分类和分析的平台
  • 批准号:
    10414891
  • 财政年份:
    2020
  • 资助金额:
    $ 55.4万
  • 项目类别:
Stellate cells and their progenitor precursors in pancreas cancer progression
胰腺癌进展中的星状细胞及其祖细胞前体
  • 批准号:
    8759844
  • 财政年份:
    2014
  • 资助金额:
    $ 55.4万
  • 项目类别:
Stellate cells and their progenitor precursors in pancreas cancer progression
胰腺癌进展中的星状细胞及其祖细胞前体
  • 批准号:
    9307750
  • 财政年份:
    2014
  • 资助金额:
    $ 55.4万
  • 项目类别:
Stellate cells and their progenitor precursors in pancreas cancer progression
胰腺癌进展中的星状细胞及其祖细胞前体
  • 批准号:
    9243147
  • 财政年份:
    2014
  • 资助金额:
    $ 55.4万
  • 项目类别:
Stellate cells and their progenitor precursors in pancreas cancer progression
胰腺癌进展中的星状细胞及其祖细胞前体
  • 批准号:
    8904631
  • 财政年份:
    2014
  • 资助金额:
    $ 55.4万
  • 项目类别:

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