Enhanced Activation and Expansion of T Cells Using Mechanically Soft Elastomer Fibers
Enhanced Activation and Expansion of T Cells Using Mechanically Soft Elastomer Fibers
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DOI：
10.1002/adbi.201700167
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发表时间：
2018-02-01
影响因子：
4.1
通讯作者：
Kam, Lance C.
中科院分区：
文献类型：
--
作者：
Dang, Alex P.;De Leo, Sarah;Kam, Lance C.
新兴的细胞疗法需要有效的平台来生产临床相关数量的高质量细胞。本报告介绍了一种基于材料的方法来改善T细胞的扩增，这是一种治疗癌症和一系列其他疾病的引人注目的药物。该系统由静电纺丝纤维组成，其呈现针对CD3和CD28的活化抗体。与目前的珠基平台相比，这些纤维在活化T细胞、启动扩增和简化细胞产物的加工方面是有效的。此外，降低这些纤维的机械刚度增强了人CD4（+）和CD8（+）T细胞混合群体的扩增，在每一轮细胞生长中提供了8倍的细胞产量。该平台还挽救了从CLL患者中分离的T细胞的扩增，这些患者通常表现出有限的反应性和其他类似衰竭的特征。通过简化细胞扩增过程和改善T细胞扩增，本文介绍的系统为细胞免疫疗法的发展提供了强大的工具。
Emerging cellular therapies require effective platforms for producing clinically relevant numbers of high-quality cells. This report introduces a materials-based approach to improving expansion of T cells, a compelling agent for treatment of cancer and a range of other diseases. The system consists of electrospun fibers, which present activating antibodies to CD3 and CD28. These fibers are effective in activating T cells, initiating expansion, and simplify processing of the cellular product, compared to current bead-base platforms. In addition, reducing the mechanical rigidity of these fibers enhances expansion of mixed populations of human CD4(+) and CD8(+) T cells, providing eightfold greater production of cells in each round of cell growth. This platform also rescues expansion of T cells isolated from CLL patients, which often show limited responsiveness and other features resembling exhaustion. By simplifying the process of cell expansion and improving T cell expansion, the system introduced here provides a powerful tool for the development of cellular immunotherapy.