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
项目成果
期刊论文数量(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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