A microbiome-informed platform for the development and testing of bacterial therapies for colorectal cancer

用于开发和测试结直肠癌细菌疗法的微生物组信息平台

基本信息

  • 批准号:
    9974305
  • 负责人:
  • 金额:
    $ 59.3万
  • 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:
    2020-05-18 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

Project Summary There is a clear imperative to develop potent, cost effective therapeutics to confront the challenge cancer poses to society. Here we address this need by developing synthetically engineered cells effective against a broad range of cancer types with a special emphasis on colorectal cancer (CRC). This cancer type is the second most common cause of cancer death in the US, with more than 50,000 Americans dying every year. Recent research demonstrates the power of genetic engineering to make significant advances towards more efficacious cancer therapy. The introduction of genetically engineered cells, such as chimeric antigen receptor T (CAR T) cells, has shown great promise for treating many types of B cell malignancies, but unfortunately targeting CAR T cells to solid tumors remains challenging. In this project we will use the tools of synthetic biology to make new engineered therapies based on bacterial rather than mammalian cells. Certain bacterial species have demonstrated a useful ability to “home in” and selectively colonize solid tumors without infecting healthy tissue. This tumor targeting property will be exploited in the proposed work to deliver safe, effective therapies directly to the locations where they are needed most: the solid core of tumors. Previously we developed a bacterial therapeutic and tested it in an animal model of metastatic disease. In contrast to other approaches utilizing bacterial cells, this “lysis strain” does not require specialized genetic modifications for the secretion of encoded cargo, it simply releases it into the environment when the cells burst. Initially we will genetically modify the lysis strain to produce a wide range of therapeutics for testing, including toxins (from bacteria, animals and plants), enzymes, antibiotics, and apoptotic peptides. Next we will analyze the tumor microbiome from human samples since we hypothesize that the native bacterial population's composition will provide a unique signature (analogous to a fingerprint) that can be used to divide tumors into distinct subtypes. We expect to use these fingerprints to identify other species with superior suitability for therapeutic delivery in treating CRC. Once identified we will develop two in vitro assays for testing the candidate strains. We will use microfluidic technology to create a high throughput co-culturing system for bacteria and a cancer cell line. In parallel, we will develop a co-culturing system for bacteria and organoids that are generated from the same human tumor samples which had been previously used for strain identification and fingerprinting. Lastly we will test the most promising therapies in an animal model of colorectal cancer to determine efficacy in a pre- clinical model.
项目总结

项目成果

期刊论文数量(0)
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专利数量(0)

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JEFF M HASTY其他文献

JEFF M HASTY的其他文献

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{{ truncateString('JEFF M HASTY', 18)}}的其他基金

Development of Engineered Native Bacteria as a Tool for Functional Manipulation of the Gut Microbiome
开发工程原生细菌作为肠道微生物组功能操纵的工具
  • 批准号:
    10737475
  • 财政年份:
    2023
  • 资助金额:
    $ 59.3万
  • 项目类别:
Reprogramming cell-fate decisions through predictive modeling and synthetic biology
通过预测模型和合成生物学重新编程细胞命运决定
  • 批准号:
    10784558
  • 财政年份:
    2022
  • 资助金额:
    $ 59.3万
  • 项目类别:
Reprogramming cell-fate decisions through predictive modeling and synthetic biology
通过预测模型和合成生物学重新编程细胞命运决定
  • 批准号:
    10344041
  • 财政年份:
    2022
  • 资助金额:
    $ 59.3万
  • 项目类别:
Reprogramming cell-fate decisions through predictive modeling and synthetic biology
通过预测模型和合成生物学重新编程细胞命运决定
  • 批准号:
    10706965
  • 财政年份:
    2022
  • 资助金额:
    $ 59.3万
  • 项目类别:
Reprogramming cell-fate decisions through predictive modeling and synthetic biology
通过预测模型和合成生物学重新编程细胞命运决定
  • 批准号:
    10908026
  • 财政年份:
    2022
  • 资助金额:
    $ 59.3万
  • 项目类别:
Design and characterization of bacterial population dynamics in solid tumor models
实体瘤模型中细菌种群动态的设计和表征
  • 批准号:
    10212134
  • 财政年份:
    2021
  • 资助金额:
    $ 59.3万
  • 项目类别:
Design and characterization of bacterial population dynamics in solid tumor models
实体瘤模型中细菌种群动态的设计和表征
  • 批准号:
    10456087
  • 财政年份:
    2021
  • 资助金额:
    $ 59.3万
  • 项目类别:
A microbiome-informed platform for the development and testing of bacterial therapies for colorectal cancer
用于开发和测试结直肠癌细菌疗法的微生物组信息平台
  • 批准号:
    10166805
  • 财政年份:
    2020
  • 资助金额:
    $ 59.3万
  • 项目类别:
A microbiome-informed platform for the development and testing of bacterial therapies for colorectal cancer
用于开发和测试结直肠癌细菌疗法的微生物组信息平台
  • 批准号:
    10397153
  • 财政年份:
    2020
  • 资助金额:
    $ 59.3万
  • 项目类别:
A microbiome-informed platform for the development and testing of bacterial therapies for colorectal cancer
用于开发和测试结直肠癌细菌疗法的微生物组信息平台
  • 批准号:
    10631898
  • 财政年份:
    2020
  • 资助金额:
    $ 59.3万
  • 项目类别:

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