Engineering and Testing of Biomimetic Stimulators for Therapeutic Applications

用于治疗应用的仿生刺激器的工程和测试

基本信息

  • 批准号:
    10570359
  • 负责人:
  • 金额:
    $ 19.19万
  • 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:
    2022-09-16 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY CD4+ T cells are the field generals of the immune system, providing instructions to innate immune cells, B cells, and other T cells to coordinate effective responses against non-self or altered-self antigens. The goal of this exploratory proposal is to advance a new class of soluble T cell engagers, which we have generated through biomimetic engineering, to redirect CD4+ T cell responses for therapeutic purposes. Normally, CD4+ T cell responses emerge from the integration of molecular interactions that occur at the interface between a CD4+ T cell and an antigen presenting cell (APC). These include but are not limited to: signals generated in response to antigenic peptides presented by MHCII molecules (pMHCII) that result from the coordinated actions of the T cell receptor (TCR), three signaling modules (CD3δε, CD3γε, CD3ζζ), and the coreceptor module CD4; interactions between LFA-1 on the T cell and ICAM-1 on the APC that provide adhesion and contribute to signaling; CD28 engagement of CD80 or CD86 on the APC that provides a critical costimulatory signal for IL-2 production and proliferation; and, CTLA-4 engagement of the same costimulatory ligands that serve to limit the magnitude of the response. The work proposed herein will explore the utility of biomimetic stimulators (BMiMS) – soluble reagents that have a novel antigen targeting region on one end and a CD4+ T cell stimulatory region on the other. The idea underlying BMiMS is that they can be used to make a target cell look like an APC and elicit physiological CD4+ T cell responses. In this proposal we will specifically work to: 1) optimize the production of BMiMS; 2) explore their functionality in vitro; and, 3) explore their functionality in vivo. The proposed work will provide us with the preliminary data needed to apply for larger proposals to further test and refine BMiMS function in vivo for use as therapeutic reagents. The long-term goal will be to initiate clinical trials to evaluate the efficacy of BMiMS as therapeutic reagents.
项目总结

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)

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Michael S Kuhns其他文献

Michael S Kuhns的其他文献

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{{ truncateString('Michael S Kuhns', 18)}}的其他基金

Engineering 2nd generation 5MCARs to monitor and treat Type-I Diabetes
设计第二代 5MCAR 来监测和治疗 I 型糖尿病
  • 批准号:
    10598106
  • 财政年份:
    2022
  • 资助金额:
    $ 19.19万
  • 项目类别:
Engineering and Testing of Biomimetic Stimulators for Therapeutic Applications
用于治疗应用的仿生刺激器的工程和测试
  • 批准号:
    10705808
  • 财政年份:
    2022
  • 资助金额:
    $ 19.19万
  • 项目类别:
Adapting 5MCAR technology for the treatment of peripheral T cell lymphoma
采用5MCAR技术治疗外周T细胞淋巴瘤
  • 批准号:
    10351121
  • 财政年份:
    2022
  • 资助金额:
    $ 19.19万
  • 项目类别:
Adapting 5MCAR technology for the treatment of peripheral T cell lymphoma
采用5MCAR技术治疗外周T细胞淋巴瘤
  • 批准号:
    10543167
  • 财政年份:
    2022
  • 资助金额:
    $ 19.19万
  • 项目类别:
Engineering 2nd generation 5MCARs to monitor and treat Type-I Diabetes
设计第二代 5MCAR 来监测和治疗 I 型糖尿病
  • 批准号:
    10435625
  • 财政年份:
    2022
  • 资助金额:
    $ 19.19万
  • 项目类别:
Inducing Tolerance with 5-Module chimeric Antigen Receptor (5MCAR) T Cells
使用 5 模块嵌合抗原受体 (5MCAR) T 细胞诱导耐受
  • 批准号:
    10247395
  • 财政年份:
    2020
  • 资助金额:
    $ 19.19万
  • 项目类别:
Development of Cellular Tools and Techniques to Identify Low Affinity T Cells
开发识别低亲和力 T 细胞的细胞工具和技术
  • 批准号:
    10259675
  • 财政年份:
    2020
  • 资助金额:
    $ 19.19万
  • 项目类别:
Development of Cellular Tools and Techniques to Identify Low Affinity T Cells
开发识别低亲和力 T 细胞的细胞工具和技术
  • 批准号:
    9974912
  • 财政年份:
    2020
  • 资助金额:
    $ 19.19万
  • 项目类别:
Probing the mechanistic basis for T cell fate decisions (R01)
探讨T细胞命运决定的机制基础(R01)
  • 批准号:
    8702920
  • 财政年份:
    2012
  • 资助金额:
    $ 19.19万
  • 项目类别:
Probing the mechanistic basis for T cell fate decisions (R01)
探讨T细胞命运决定的机制基础(R01)
  • 批准号:
    10088367
  • 财政年份:
    2012
  • 资助金额:
    $ 19.19万
  • 项目类别:

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