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:Imaging CAR-T Synapse as a Quality Control for CAR Engineering.
Imaging CAR-T Synapse as a Quality Control for CAR Engineering.
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嵌合抗原受体(CAR)已发展成为重编程T细胞以实现靶向杀伤的强大工具。CAR-T 疗法在治疗某些类型的血液肿瘤中取得了成功,其应用目前正扩展至实体瘤、自身免疫性疾病、病毒感染和纤维化。这些应用需要设计大量靶向多种抗原的新型CAR。在此,我们描述了两种作为新开发CAR验证质量控制的方法:(1)细胞间偶联实验,反映CAR在细胞环境中与抗原的有效结合;(2)突触中CD45的排除,作为CAR信号传导潜力的指示。这些实验检测了功能性CAR-T 的先决条件,并揭示了CAR-T 激活无效的原因。
The chimeric antigen receptor (CAR) evolves as a powerful tool to reprogram T cells for targeted killing. CAR-T therapy succeeded in treating certain types of blood cancers, and its application is now expanding towards solid tumors, autoimmune diseases, viral infection, and fibrosis. These require the design of a large number of new CARs that target a variety of antigens.
Here we described two methods as a quality control for validating newly developed CARs: (1) the cell-cell conjugation assay as a reflection of efficient binding of CAR to antigen in the cellular context and (2) CD45 exclusion in the synapse as an indication of CAR signaling potential. These assays examine prerequisites for a functional CAR-T and reveal causes for ineffective CAR-T activation.
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