A micro-dissection platform for generating uniform-sized patient-derived tumor organoids (PDOs) for personalized cancer therapy

一个显微解剖平台,用于生成大小一致的患者来源的肿瘤类器官(PDO),用于个性化癌症治疗

基本信息

  • 批准号:
    10697348
  • 负责人:
  • 金额:
    $ 17.93万
  • 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:
    2022-09-05 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary Patient-derived tumor organoids (PDO), involving the ex vivo culture of fresh tumor fragments, have emerged as promising models for predicting patient drug response for personalized cancer therapy. PDOs recapitulate the tumor micro-environment (TME), resemble the source tumor phenotypically and genomically, and are compatible with high-throughput drug screening. However, the lack of preservation of immune cells in PDOs has been a major roadblock to modeling immunotherapy. Our team recently demonstrated a new type of PDO that cultures tumor fragments as a cohesive unit, allowing the in situ preservation of diverse immune cell types alongside tumor cells without artificial reconstitution. This approach has enabled the modeling of patient-specific responses to immune checkpoint inhibitors. One of the first steps in the generation of PDOs is the dissection of patient tumor specimen into small fragments. Mechanical dissection, instead of enzymatic digestion, is critical in preserving the in vivo association between tumor cells and endogenous immune and non-immune elements. The ability to preserve endogenous immune cells, including tumor-infiltrating lymphocytes (TIL), is particularly important for personalized immunotherapy testing. However, current mechanical dissection relies primarily on manual mincing of tumor specimen into small fragments. It results in fragments with a broad size range, and is imprecise and irreproducible. Fragments that are too large suffer from inadequate nutrient supply, suboptimal oxygenation and viability, and poor drug penetration. Fragments that are too small are unlikely to preserve sufficient stromal cells to support PDO growth, and/or endogenous immune cells which may be present at low concentrations. As such, there is an unmet need for a better way to generate tumor fragments of controllable and uniform size, and identify optimal size(s) to increase the reproducibility and yield of viable PDOs that can preserve the cellular contexture and tumor architecture. This project aims to address this need by developing a new method to mechanically dissect tumor specimen into uniform fragments. Performance measures include fragment size uniformity, PDO viability, preservation of immune cells, and tumor cytotoxicity in response to immunotherapy. Other cutting methods including manual mincing will be used as benchmarks.
项目总结

项目成果

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Sindy Kam-Yan Tang其他文献

Sindy Kam-Yan Tang的其他文献

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{{ truncateString('Sindy Kam-Yan Tang', 18)}}的其他基金

An integrated microtechnology platform for spatially resolved mass spectrometry-based proteomics
用于基于空间分辨质谱的蛋白质组学的集成微技术平台
  • 批准号:
    10564117
  • 财政年份:
    2023
  • 资助金额:
    $ 17.93万
  • 项目类别:
Probing basophil function in microfluidic systems for allergic disease diagnosis
探测微流体系统中的嗜碱性粒细胞功能以诊断过敏性疾病
  • 批准号:
    10636914
  • 财政年份:
    2021
  • 资助金额:
    $ 17.93万
  • 项目类别:
Probing basophil function in microfluidic systems for allergic disease diagnosis
探测微流体系统中的嗜碱性粒细胞功能以诊断过敏性疾病
  • 批准号:
    10457438
  • 财政年份:
    2021
  • 资助金额:
    $ 17.93万
  • 项目类别:
Probing basophil function in microfluidic systems for allergic disease diagnosis
探测微流体系统中的嗜碱性粒细胞功能以诊断过敏性疾病
  • 批准号:
    10302059
  • 财政年份:
    2021
  • 资助金额:
    $ 17.93万
  • 项目类别:

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