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用分支过程预测嵌合抗原受体T细胞(CAR-T)对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的作用

Forecasting the action of CAR-T cells against SARS-corona virus-II infection with branching process.

作者信息

Al-Utaibi Khaled A, Nutini Alessandro, Sohail Ayesha, Arif Robia, Tunc Sümeyye, Sait Sadiq M

机构信息

Computer Science and Software Engineering Department, University of Ha'il, Ha'il, Saudi Arabia.

Centro Studi Attività Motorie, Department of Biology and Biomechanics, 94 via di Tiglio, loc. Arancio, 55100 Lucca, Italy.

出版信息

Model Earth Syst Environ. 2022;8(3):3413-3421. doi: 10.1007/s40808-021-01312-3. Epub 2021 Oct 15.

Abstract

The CAR-T cells are the genetically engineered T cells, designed to work specifically for the virus antigens (or other antigens, such as tumour specific antigens). The CAR-T cells work as the living drug and thus provides an adoptive immunotherapy strategy. The novel corona virus treatment and control designs are still under clinical trials. One of such techniques is the injection of CAR-T cells to fight against the COVID-19 infection. In this manuscript, the hypothesis is based on the CAR-T cells, that are suitably engineered towards SARS-2 viral antigen, by the N protein. The N protein binds to the SARS-2 viral RNA and is found in abundance in this virus, thus for the engineered cell research, this protein sequence is chosen as a potential target. The use of the sub-population of T-reg cells is also outlined. Mathematical modeling of such complex line of action can help to understand the dynamics. The modeling approach is inspired from the probabilistic rules, including the branching process, the Moran process and kinetic models. The Moran processes are well recognized in the fields of artificial intelligence and data science. The model depicts the infectious axis "virus-CAR-T cells-memory cells". The theoretical analysis provides a positive therapeutic action; the delay in viral production may have a significant impact on the early stages of infection. Although it is necessary to carefully evaluate the possible side effects of therapy. This work introduces the possibility of hypothesizing an antiviral use by CAR-T cells.

摘要

嵌合抗原受体T细胞(CAR-T细胞)是经过基因工程改造的T细胞,旨在专门针对病毒抗原(或其他抗原,如肿瘤特异性抗原)发挥作用。CAR-T细胞作为一种活体药物,从而提供了一种过继性免疫治疗策略。新型冠状病毒的治疗和控制方案仍在临床试验中。其中一种技术是注射CAR-T细胞来对抗新冠病毒感染。在本论文中,假设基于通过N蛋白对针对SARS-CoV-2病毒抗原进行适当工程改造的CAR-T细胞。N蛋白与SARS-CoV-2病毒RNA结合,并且在这种病毒中大量存在,因此在工程细胞研究中,选择该蛋白序列作为潜在靶点。还概述了调节性T细胞亚群的使用。对这种复杂作用过程进行数学建模有助于理解其动态变化。该建模方法受到概率规则的启发,包括分支过程、莫兰过程和动力学模型。莫兰过程在人工智能和数据科学领域中得到了广泛认可。该模型描绘了“病毒-CAR-T细胞-记忆细胞”的感染轴。理论分析提供了积极的治疗作用;病毒产生的延迟可能对感染早期阶段产生重大影响。尽管有必要仔细评估治疗可能产生的副作用。这项工作介绍了假设CAR-T细胞具有抗病毒用途的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3642/8516624/12ce572f5195/40808_2021_1312_Fig1_HTML.jpg

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