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
- 来源:
- 关键词:ActinsAddressAdoptive ImmunotherapyAffectAntigen-Presenting CellsBindingBiocompatible MaterialsCAR T cell therapyCD28 geneCD3 AntigensCaliberCell Culture TechniquesCell physiologyCellsCellular immunotherapyChemicalsCommunicationComplexDevelopmentDimensionsDiseaseElastomersElectrospinningEngineeringEnvironmentExcisionFiberFutureGenerationsGeometryGoalsHumanImageImmunotherapyIndividualKnowledgeLeadLengthLigandsMalignant NeoplasmsMechanicsMicrofabricationModulusMolecularPatientsPharmaceutical PreparationsPharmacologyPlayProductionResearchRoleSeriesSignal TransductionStructureSurfaceSystemT cell responseT-Cell ActivationT-LymphocyteTechnologyTestingTherapeutic InterventionTissue Engineeringbasecancer therapycell growthcostdesignexperimental studyextracellularfiber cellimprovedinsightinterestmechanical forcemechanical propertiesmechanotransductionpolymerizationpublic health relevanceresponsetool
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细胞和抗原提呈细胞之间的通讯中起着关键作用
(APCS)。我们课题组之前的研究表明,T细胞可以感知并对
TCR/CD3和CD28的活化底物的机械刚性,本质上是一种
工程化APC。这一发现导致了改进人类T细胞生产的新系统
免疫疗法。特别是,基于软弹性体纤维的系统每轮产生更多的细胞
比刚性对应物扩增,也挽救了正在接受治疗的个体的细胞扩增
癌症。然而,这些先前的实验也表明,潜在的机械感觉反应是
不仅取决于材料的体积模数,而且还取决于其结构,其规模可与之媲美,甚至可以媲美
比附着的细胞大。这一探索性/开发性项目的总体目的是
确定该网状平台的哪些特征,例如纤维直径和/或跨度长度会影响T细胞
机械传感。这将通过两个相辅相成的具体目标来实现。在第一,一套战略性的
独立地改变感兴趣的多个参数的光纤几何形状将通过进一步
发展电纺和微细加工弹性体。多种T细胞免疫应答的比较
这些纤维将被用来分离和量化每个参数的影响。第二个具体目标
聚焦于附着的T细胞,描述导致力产生的内部组件的特征。一起,
这些研究将解决目前关于T细胞如何机械地相互作用的知识空白
地形复杂的底物,提供了对这些细胞如何识别和攻击目标的洞察
改善新兴的细胞免疫治疗市场的细胞和策略。
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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Lance C Kam其他文献
Lance C Kam的其他文献
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{{ 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:
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