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DNA 折纸组装球状体用于评估嵌合抗原受体巨噬细胞(CAR-M)的细胞毒性与浸润

英文原题:DNA origami assembled spheroid for evaluating cytotoxicity and infiltration of chimeric antigen receptor macrophage (CAR-M).

查看英文原题

DNA origami assembled spheroid for evaluating cytotoxicity and infiltration of chimeric antigen receptor macrophage (CAR-M).

PubMed 2024/10/11(内容时间) Commun Biol Q1 · IF 5.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T 细胞治疗血液系统恶性肿瘤取得了显著成果,但治疗实体瘤的成功有限。作为 CAR 治疗的另一种候选方案,CAR 巨噬细胞(CAR-M)可在肿瘤相关抗原(TAA)的引导下被激活并吞噬肿瘤,显示出治疗实体瘤的潜力。然而,CAR 引导 CAR-M 趋化和侵袭肿瘤的机制仍知之甚少。本研究利用新型自组装核酸纳米结构装饰的活细胞(NAC)构建三维肿瘤球体,探究 CAR 在 CAR-M 黏附和浸润中的作用。结果显示,CAR-M 在二维模型和三维肿瘤球体中均表现出更强的侵袭和杀伤能力。总之,基于三维 NAC 组装的肿瘤球体模型可作为适用于 CAR-M 靶点筛选和药效学评估的平台。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapies have shown remarkable results in patients with hematological malignancies.

However, their success in treating solid tumors has been limited. As an alternative candidate for the CAR therapy, CAR-macrophages (CAR-M) have demonstrated activation and phagocytosis directed by tumor-associated antigen (TAA), showing promise in the treatment of solid tumors.

Nevertheless, the mechanisms by which CARs direct tumor chemotaxis and invasion of CAR-M remain poorly understood. In this study, we aim to investigate the role of CARs in CAR-M attachment and infiltration using 3D tumor spheroids, which were created by utilizing a novel self-assembling nucleic acid nanostructure decorated living cells (NAC).

Our results demonstrated that CAR-M exhibited higher invasion and killing capacity in 2D model and 3D tumor spheroids. In summary, the 3D NAC assembled tumor spheroid model provides a suitable platform for target screening and pharmacodynamic evaluation of CAR-M.

论文信息

作者
Zhu Q、He X、Liu J、Wang H、Shan X、Song G、Zhang L、Zhao Y
第一作者单位
RocRock Biotechnology Co. Ltd, Suzhou, China.China
通讯作者单位
RocRock Biotechnology Co. Ltd, Suzhou, China. xiushanyin@me.com.China
文献类型
非美国政府资助研究
期刊
Communications biology2024 Oct 11
原文标识
PubMed 39390143 · DOI 10.1038/s42003-024-07009-4