T Cell Mechanosensing of Microscale Fibers

微型纤维的 T 细胞机械传感

基本信息

  • 批准号:
    9917202
  • 负责人:
  • 金额:
    $ 24.3万
  • 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:
    2019-12-24 至 2021-11-30
  • 项目状态:
    已结题

项目摘要

Abstract Mechanical forces play critical roles in communication between T cells and Antigen Presenting Cells (APCs). Previous studies from our research group demonstrated that T cells can sense and respond to the mechanical rigidity of an activating substrate presenting ligands to TCR/CD3 and CD28, essentially an engineered APC. This discovery led to new systems for improving production of human T cells for cellular immunotherapy. In particular, a system based on soft elastomer fibers produced more cells per round of expansion than a rigid counterpart, and also rescued expansion of cells from individuals being treated for cancer. However, these previous experiments also suggested that the underlying mechanosensing response is dependent on not only the bulk modulus of the material but also its structure at scales comparable to or even larger than that of the attached cells. The overall purpose of this exploratory / developmental project is to identify what features of this mesh platform, such as fiber diameter and/or span length influence T cell mechanosensing. This will be approached in two complementary Specific Aims. In the first, a strategic set of fiber geometries that independently vary the multiple parameters of interest will be created by further developing electrospinning and microfabrication of elastomers. Comparison of multiple T cell responses to these fibers will be used to separate and quantify the effects of each parameter. The second Specific Aim focuses on the adherent T cell, characterizing the internal assemblies that lead to force generation. Together, these studies will address the current gap in knowledge of how T cells mechanically interact with topographically complex substrates, providing both insights into how these cells recognize and attack target cells and strategies to improve the emerging cellular immunotherapy market.
摘要 机械力在T细胞和抗原呈递细胞之间的通讯中起关键作用 (APC)。我们研究小组以前的研究表明,T细胞可以感知并响应 活化底物呈递TCR/CD 3和CD 28配体的机械刚性,基本上是 工程APC这一发现导致了新的系统,用于改善人类T细胞的生产, 免疫疗法特别地,基于软弹性体纤维的系统每轮产生更多的细胞, 扩张比刚性对应物,并且还挽救了来自被治疗的个体的细胞的扩张。 癌然而,这些先前的实验还表明,潜在的机械感测响应是 不仅取决于材料的体积模量,而且还取决于其结构, 比附着的细胞大。这个探索/发展项目的总体目的是 确定该网状物平台的哪些特征,例如纤维直径和/或跨度长度影响T细胞 机械感应这将在两个互补的具体目标中进行。首先,一套战略性的 将通过进一步的方法产生独立地改变多个感兴趣参数的纤维几何形状 开发弹性体的静电纺丝和微细加工。多种T细胞应答的比较 这些纤维将用于分离和量化每个参数的影响。第二个具体目标 重点是粘附T细胞,表征导致力产生的内部组件。我们一起努力, 这些研究将解决目前在T细胞如何机械相互作用方面的知识空白, 地形复杂的基板,提供了深入了解这些细胞如何识别和攻击目标, 细胞和策略,以改善新兴的细胞免疫治疗市场。

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 }}

Lance C Kam其他文献

Lance C Kam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('Lance C Kam', 18)}}的其他基金

Microscale System for Functional T Cell Transcriptomics
功能性 T 细胞转录组学微型系统
  • 批准号:
    10156792
  • 财政年份:
    2020
  • 资助金额:
    $ 24.3万
  • 项目类别:
Microscale System for Functional T Cell Transcriptomics
功能性 T 细胞转录组学微型系统
  • 批准号:
    10319619
  • 财政年份:
    2020
  • 资助金额:
    $ 24.3万
  • 项目类别:
Controllable Rigidity Surfaces for T Cell Mechanobiology
T 细胞力学生物学的可控刚性表面
  • 批准号:
    9243969
  • 财政年份:
    2016
  • 资助金额:
    $ 24.3万
  • 项目类别:
Sample Sparing Chambers for Imaging of T cell Response and Function
用于 T 细胞反应和功能成像的样品备用室
  • 批准号:
    9094442
  • 财政年份:
    2015
  • 资助金额:
    $ 24.3万
  • 项目类别:
Advanced Rigidity-based Material for Enhanced Immunotherapy
用于增强免疫治疗的先进刚性材料
  • 批准号:
    9182814
  • 财政年份:
    2014
  • 资助金额:
    $ 24.3万
  • 项目类别:
Spatial coordination of CD28 and TCR signaling
CD28 和 TCR 信号传导的空间协调
  • 批准号:
    8261369
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Direct Write Microfabrication Platform for Biomedical Research
用于生物医学研究的直写微加工平台
  • 批准号:
    7794375
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Spatial coordination of CD28 and TCR signaling
CD28 和 TCR 信号传导的空间协调
  • 批准号:
    8067010
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Spatial coordination of CD28 and TCR signaling
CD28 和 TCR 信号传导的空间协调
  • 批准号:
    8463106
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Spatial coordination of CD28 and TCR signaling
CD28 和 TCR 信号传导的空间协调
  • 批准号:
    7993457
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.3万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了