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泛血液系统肿瘤嵌合抗原受体(CAR)T 细胞治疗反应的预测性生物标志物

英文原题:Predictive biomarkers of response to chimeric antigen receptor (CAR) T-cell therapy for pan-haematologic cancer.

查看英文原题

Predictive biomarkers of response to chimeric antigen receptor (CAR) T-cell therapy for pan-haematologic cancer.

PubMed 2026/03/09(内容时间) Nat Biomed Eng Q1 · IF 26.3(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法对癌症患者具有巨大前景,而识别预测性生物标志物对于寻找指导治疗的新方法至关重要。信息学和机器学习在CAR-T 细胞疗法中应用的主要挑战包括样本量有限以及不同癌症适应症和试验之间数据生成的不一致性。在此,我们采用了全球性、泛血液系统癌症的方法,分析了跨越5种癌症类型和13项临床试验的256例患者。我们使用一个框架生成数据,该框架包括输注前临床特征、通过流式细胞术使用17种独特标志物分析的超过200万个单采T细胞、CAR-T 细胞制造过程中的离体T细胞扩增、30种血清标志物的超过90,000次测量,以及使用qPCR对循环CAR-T 细胞进行连续追踪。基于这一数据资源,我们展示了泛癌预测性生物标志物的潜力,这些标志物能够捕捉CAR-T 细胞疗法中治疗应答和无应答的可推广特征。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy holds great promise for patients with cancer, and the identification of predictive biomarkers is crucial in finding new ways to guide therapy. Major challenges to the application of informatics and machine learning in CAR T-cell therapy include limited sample sizes and non-uniformity in data generation across cancer indications and trials.

Here we took a global, pan-haematologic cancer approach, analysing 256 patients across 5 cancer types and 13 clinical trials.

We generated data using a framework that included pre-infusion clinical features, over 2 million apheresis T cells analysed by flow cytometry using 17 unique markers, ex vivo T-cell expansion during CAR T-cell manufacture, more than 90,000 measurements of 30 serum markers and serial tracking of circulating CAR T cells using qPCR. From this data resource, we demonstrate the potential of pan-cancer predictive biomarkers that capture generalizable characteristics of treatment response and non-response in CAR T-cell therapy.

论文信息

作者
Chen GM、Jain A、Gering DT、Satulovsky J、Datta S、Lai P、Karar J、Gonzalez VE
第一作者单位
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. gregory.chen@pennmedicine.upenn.edu.United States
通讯作者单位
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jfrai@upenn.edu.United States
期刊
Nature biomedical engineering2026 Apr
原文标识
PubMed 41803255 · DOI 10.1038/s41551-026-01633-7