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The therapeutic landscape for cells engineered with chimeric antigen receptors
Nature Biotechnology ( IF 46.9 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41587-019-0329-2
Matthew MacKay 1, 2, 3, 4 , Ebrahim Afshinnekoo 1, 2, 3 , Jonathan Rub 1, 3 , Ciaran Hassan 5 , Mihir Khunte 5 , Nithyashri Baskaran 5 , Bryan Owens 5 , Lauren Liu 5 , Gail J Roboz 6 , Monica L Guzman 6 , Ari M Melnick 6 , Shixiu Wu 7, 8 , Christopher E Mason 1, 2, 3, 9
Affiliation  

Despite the global rapid increase in the number of clinical trials employing chimeric antigen receptors (CARs), no comprehensive survey of their scope, targets and design exists. In this study, we present an interactive CAR clinical trial database, spanning 64 targets deployed in T cells (CAR-T), natural killer cells (CAR-NK) or mixtures (CAR-NK/T) from over 500 clinical trials in 20 countries, encompassing >20,000 patients. By combining these data with transcriptional and proteomic data, we create a ‘targetable landscape’ for CAR cell therapies based on 13,206 proteins and RNAs across 78 tissues, 124 cell types and 20 cancer types. These data suggest a landscape of over 100 single targets and over 100,000 target pairs using logical switches for CAR cell engineering. Our analysis of the CAR cellular therapeutic landscape may aid the design of future therapies, improve target-to-patient matching, and ultimately help inform our understanding of CAR therapy’s safety and efficacy.



中文翻译:

用嵌合抗原受体工程化的细胞的治疗前景

尽管全球使用嵌合抗原受体(CAR)的临床试验数量迅速增加,但尚未对其范围、目标和设计进行全面调查。在这项研究中,我们提出了一个交互式 CAR 临床试验数据库,涵盖 20 个国家/地区 500 多个临床试验中部署在 T 细胞 (CAR-T)、自然杀伤细胞 (CAR-NK) 或混合物 (CAR-NK/T) 中的 64 个靶标。个国家,涵盖超过 20,000 名患者。通过将这些数据与转录和蛋白质组数据相结合,我们基于 78 种组织、124 种细胞类型和 20 种癌症类型的 13,206 种蛋白质和 RNA,为 CAR 细胞疗法创建了“可靶向景观”。这些数据表明,使用逻辑开关进行 CAR 细胞工程时,有超过 100 个单一目标和超过 100,000 个目标对。我们对 CAR 细胞治疗前景的分析可能有助于未来疗法的设计,改善目标与患者的匹配,并最终帮助我们了解 CAR 疗法的安全性和有效性。

更新日期:2020-01-06
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