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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:In Vitro Screening Assay for Activators of T-Cell Migration to Solid Tumors.
In Vitro Screening Assay for Activators of T-Cell Migration to Solid Tumors.
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近年来,嵌合抗原受体(CAR)T细胞疗法已开始用于胶质母细胞瘤等实体瘤。儿童恶性脑肿瘤患者在接受强化多模式根治性治疗后会出现广泛的长期并发症。CAR-T 细胞治疗有可能产生有利的结局并降低当前治疗的毒性。实体瘤的T细胞浸润与良好预后相关。针对实体瘤的CAR-T 细胞治疗中一个在很大程度上被忽视的领域是增强CAR-T 细胞迁移和浸润实体瘤的能力。一个可能的原因是缺乏标准化的体外试验,这些试验可以筛选出在CAR-T 细胞治疗中导致T细胞迁移增强的基因修饰。我们报告了一种新型共培养试验,使用3D肿瘤球体与T细胞共培养,通过简单的基于成像的读数来分析激活CAR-T 细胞的干预措施对细胞迁移的影响。该试验可应用于几种不同的癌细胞系,并具有更高的通量,还可用于测量目前可用的CAR-T 细胞疗法在未经测试的实体瘤中的效率。
Recently, chimeric antigen receptor (CAR) T-cell therapy has begun to be used for solid tumors such as glioblastoma multiforme. Pediatric malignant brain tumors patients develop extensive long-term morbidity of intensive multimodal curative treatment. CAR T-cells treatments could potentially create favorable outcomes and reduce the toxicity of current treatment.
T-cell infiltration of solid tumors has been associated with good prognosis. A largely overlooked area of CAR T-cell therapy targeting solid tumors is enhancing the ability of CAR T-cells to migrate and infiltrate solid tumors. A potential reason could be lack of standard in vitro assays which can screen for genetic modifications that result in enhanced T-cell migration in CAR T-cell therapies.
We report a novel coculture assay using 3D tumor spheroids cocultured with T-cells to analyze the effect of activating CAR T-cell interventions on cell migration by a simple imaging based readout. This assay can be applied to several different kinds of cancer cell lines in higher throughput as well as toward measuring the efficiency of currently available CAR T-cell therapies in untested solid tumors.
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