患者的个性化免疫治疗:用人工智能通过单细胞RNA-seq进行定义。

Medical research archives Pub Date : 2023-08-01 Epub Date: 2023-08-30 DOI:10.18103/mra.v11i8.4293
Biaoru Li
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摘要

免疫治疗,包括免疫细胞治疗和靶向治疗,是通过不断发现分子化合物或免疫细胞而逐渐发展起来的。选择最佳的一种或靶化合物与免疫细胞治疗的最佳组合对临床科学家和临床医生来说是一项挑战。我们发现,在肿瘤浸润性淋巴细胞(TIL)治疗后,个体疗效各不相同,现在在一组异质性免疫细胞中发现了TIL。为了为每位患者选择最佳的免疫疗法,我们开始研究TIL基因组学,包括2007年发表的TIL单细胞mRNA差异显示和2013年发表的TIL单细胞RNA-seq,2015年建立了TIL定量网络,2022年研究了免疫治疗的机器学习模型。这些手册报告了单细胞RNA-seq数据与机器学习相结合,以评估个体患者的最佳化合物和免疫细胞。机器学习模型是人工智能的一种,可以从单细胞RNA-seq中估计靶向基因组的差异,从而涵盖13种免疫细胞疗法和正在进行的FDA批准的靶向疗法,如PD1抑制剂、PDL1抑制剂和CTLA4抑制剂,以及其他不同的治疗方法,如HDACI或DNMT1抑制剂,FDA批准的药物。此外,还涵盖临床试验的1期、2期、3期和4期,如TIL、CAR T细胞、TCR T细胞。带有人工智能估计系统的单细胞RNA-seq比我们发表的微阵列或细胞治疗模型要好得多。医学目标是解决临床免疫治疗中的三个问题:提高疗效;临床应用中不良反应的减少和成本的降低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Personalized Immunotherapy of Patients: Defining by Single-cell RNA-seq with Artificial Intelligence.

Immunotherapy, including immune cell therapy and targeted therapy, is gradually developed through the ongoing discovery of molecular compounds or immune cells. Choosing the best one or the best combination of target compounds and immune-cell therapy is a challenge for clinical scientists and clinicians. We have found variable efficacy individually after tumor-infiltrating lymphocyte (TIL) therapy, and now TILs have been discovered in a group of heterogeneous immune cells. To select the best immunotherapy for each patient, we started to study TIL genomics, including single-cell mRNA differential display from TIL published in 2007 and single-cell RNA-seq from TIL published in 2013, set up TIL quantitative network in 2015, researched machine-learning model for immune therapy in 2022. These manual reports single-cell RNA-seq data combined with machine learning to evaluate the optimal compounds and immune cells for individual patients. The machine-learning model, one of artificial intelligence, can estimate targeting genomic variance from single-cell RNA-seq so that they can cover thirteen kinds of immune cell therapies and ongoing FDA-approved targeted therapies such as PD1 inhibitors, PDL1 inhibitors, and CTLA4 inhibitors, as well as other different treatments such as HDACI or DNMT1 inhibitors, FDA-approved drugs. Moreover, also cover Phase-1, Phase-2, Phase-3, and Phase-4 of clinical trials, such as TIL, CAR T-cells, TCR T-cells. Single-cell RNA-seq with an Artificial intelligence estimation system is much better than our published models from microarrays or just cell therapy. The medical goal is to address three issues in clinical immunotherapy: the increase of efficacy; the decrease of adverse effects and the decrease of the cost in clinical applications.

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