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用于体外评估 CAR-T 细胞治疗的缺氧 3D 肿瘤模型

英文原题:Hypoxic 3D Tumor Model for Evaluating of CAR-T Cell Therapy In Vitro.

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Hypoxic 3D Tumor Model for Evaluating of CAR-T Cell Therapy In Vitro.

PubMed 2024/01/01(内容时间) Methods Mol Biol

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中文摘要

实体瘤存在异常的物理和生化屏障,会妨碍嵌合抗原受体(CAR)T细胞疗法发挥作用。然而,人们对实体瘤微环境(例如缺氧)如何调节CAR-T 细胞功能尚缺乏了解。缺氧是许多晚期实体瘤的常见特征,可促使癌细胞和T细胞的代谢、表型及相互作用发生重塑。为了解CAR-T 细胞在实体瘤中的活性,并评估包含CAR-T 细胞的新型联合治疗效果,需要建立能够忠实模拟生理相关肿瘤微环境下CAR-T 细胞与实体瘤相互作用的体外模型。本文展示如何使用无需洁净室、基于微铣削的微器件建立缺氧三维(3-D)肿瘤模型,并评估CAR-T 细胞联合PD-1/PD-L1抑制的疗效。

展开英文摘要原文

Solid tumors contain abnormal physical and biochemical barriers that hinder chimeric antigen receptor (CAR) T cell therapies.

However, there is a lack of understanding on how the solid tumor microenvironment (e. g. hypoxia) modulates CAR-T cell function. Hypoxia is a common feature of many advanced solid tumors that contributes to reprogramming of cancer and T cell metabolism as well as their phenotypes and interactions.

To gain insights into the activities of CAR-T cells in solid tumors and to assess the effectiveness of new combination treatments involving CAR-T cells, in vitro models that faithfully reflect CAR-T cell-solid tumor interactions under physiologically relevant tumor microenvironment is needed.

Here we demonstrate how to establish a hypoxic 3-dimensional (3-D) tumor model using a cleanroom-free, micromilling-based microdevice and assess the efficacy of the combination treatment with CAR-T cells and PD-1/PD-L1 inhibition.

论文信息

作者
Oh JM、Shen K
第一作者单位
Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.United States
通讯作者单位
Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. keyue.shen@usc.edu.United States
文献类型
非美国政府资助研究 · 美国 NIH 院内研究
期刊
Methods in molecular biology (Clifton, N.J.)2024
原文标识
PubMed 38070112 · DOI 10.1007/978-1-0716-3593-3_10