权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
Lance C Kam
金额：
$ 24.3万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
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：
https://reporter.nih.gov/project-details/9917202
关键词：
Actins Address Adoptive Immunotherapy Affect Antigen-Presenting Cells Binding Biocompatible Materials CAR T cell therapy CD28 gene CD3 Antigens Caliber Cell Culture Techniques Cell physiology Cells Cellular immunotherapy Chemicals Communication Complex Development Dimensions Disease Elastomers Electrospinning Engineering Environment Excision Fiber Future Generations Geometry Goals Human Image Immunotherapy Individual Knowledge Lead Length Ligands Malignant Neoplasms Mechanics Microfabrication Modulus Molecular Patients Pharmaceutical Preparations Pharmacology Play Production Research Role Series Signal Transduction Structure Surface System T cell response T-Cell Activation T-Lymphocyte Technology Testing Therapeutic Intervention Tissue Engineering base cancer therapy cell growth cost design experimental study extracellular fiber cell improved insight interest mechanical force mechanical properties mechanotransduction polymerization public health relevance response tool

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