CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:DNA origami assembled spheroid for evaluating cytotoxicity and infiltration of chimeric antigen receptor macrophage (CAR-M).
DNA origami assembled spheroid for evaluating cytotoxicity and infiltration of chimeric antigen receptor macrophage (CAR-M).
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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。
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.
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