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:Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function.
Jurkat T-cell lines exhibit marked genomic instability affecting karyotype, mutational profile, gene expression, immunophenotype and function.
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Jurkat细胞系来源于一例T细胞淋巴母细胞白血病,被广泛用作生物医学研究中的模型T细胞,包括用于CAR-T 细胞等细胞疗法的临床前表征。
在此,我们对来自三个不同实验室的Jurkat克隆E6-1细胞的基因组、转录组和功能特征进行了表征,并将其与来自美国典型培养物保藏中心(ATCC)的Jurkat E6-1细胞进行了比较。
我们发现了Jurkat E6-1群体之间及群体内部存在显著的核型异质性,并通过染色体微阵列分析予以确认。对每个细胞群体进行的全外显子组测序揭示了共有和独特的突变谱,且Jurkat E6-1细胞群体之间的转录组谱也存在显著差异。
最后,Jurkat E6-1细胞群体在免疫表型和细胞因子产生方面表现出显著差异,这与所观察到的基因型和转录组变化相一致。
总之,我们发现了Jurkat E6-1细胞群体之间及群体内部存在显著的基因组异质性,突显了该细胞系的基因组不稳定性。这些基因组变化与蛋白质表达和细胞因子产生的差异相关,可能影响功能检测。
我们的发现强调了监测细胞传代次数、表征细胞系以及更换细胞系库存的重要性,以确保使用Jurkat E6-1细胞进行的检测的准确性、可重复性和可转化性。
The Jurkat cell line, derived from a case of T-cell lymphoblastic leukaemia, is widely employed as a model T-cell for biomedical research, including for the preclinical characterisation of cellular therapies such as chimeric antigen receptor T-cells.
Here, we characterised genomic, transcriptomic, and functional features of Jurkat clone E6-1 cells from three different laboratories and compared these with Jurkat E6-1 cells from the American Type Culture Collection (ATCC).
We identified marked karyotypic heterogeneity both between and within Jurkat E6-1 populations, confirmed through chromosomal microarray. Whole exome sequencing of each cell population revealed both shared and unique mutational profiles, and transcriptomic profiles varied markedly between Jurkat E6-1 cell populations.
Finally, the Jurkat E6-1 cell populations exhibited substantial variations in immunophenotype and cytokine production, which were consistent with the genotypic and transcriptomic changes observed. In summary, we identify substantial genomic heterogeneity both between and within Jurkat E6-1 cell populations, highlighting the genomic instability of this line. These genomic changes were associated with differences in protein expression and cytokine production that may affect functional assays.
Our findings highlight the importance of monitoring cell passage number, characterising cell lines, and replacing cell line stocks to assure the accuracy, reproducibility, and translatability of assays employing Jurkat E6-1 cells.
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