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嵌合抗原受体T细胞(CAR-T)疗法中的数学模型与计算方法。

Mathematical models and computational approaches in CAR-T therapeutics.

作者信息

Putignano Guido, Ruipérez-Campillo Samuel, Yuan Zhou, Millet José, Guerrero-Aspizua Sara

机构信息

bioERGOtech, Taranto, Italy.

Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.

出版信息

Front Immunol. 2025 Aug 1;16:1581210. doi: 10.3389/fimmu.2025.1581210. eCollection 2025.

Abstract

BACKGROUND

The field of synthetic biology aims to engineer living organisms for specific therapeutic applications, with CAR-T cell therapy emerging as a groundbreaking approach in cancer treatment due to its potential for flexibility, specificity, predictability, and controllability. CAR-T cell therapies involve the genetic modification of T cells to target tumor-specific antigens. However, challenges persist because the limited spatio-temporal resolution in current models hinders the therapy's safety, cost-effectiveness, and overall potential, particularly for solid tumors.

MAIN BODY

This manuscript explores how mathematical models and computational techniques can enhance CAR-T therapy design and predict therapeutic outcomes, focusing on critical factors such as antigen receptor functionality, treatment efficacy, and potential adverse effects. We examine CAR-T cell dynamics and the impact of antigen binding, addressing strategies to overcome antigen escape, cytokine release syndrome, and relapse.

CONCLUSION

We propose a comprehensive framework for using these models to advance CAR-T cell therapy, bridging the gap between existing therapeutic methods and the full potential of CAR-T engineering and its clinical application.

摘要

背景

合成生物学领域旨在对活生物体进行工程改造以用于特定的治疗应用,嵌合抗原受体T细胞(CAR-T)疗法因其具有灵活性、特异性、可预测性和可控性的潜力,成为癌症治疗中的一种开创性方法。CAR-T细胞疗法涉及对T细胞进行基因改造以靶向肿瘤特异性抗原。然而,挑战依然存在,因为当前模型中有限的时空分辨率阻碍了该疗法的安全性、成本效益和整体潜力,尤其是对于实体瘤而言。

主体

本手稿探讨了数学模型和计算技术如何能够增强CAR-T疗法的设计并预测治疗结果,重点关注抗原受体功能、治疗效果和潜在不良反应等关键因素。我们研究了CAR-T细胞动力学以及抗原结合的影响,探讨了克服抗原逃逸、细胞因子释放综合征和复发的策略。

结论

我们提出了一个使用这些模型推进CAR-T细胞疗法的综合框架,弥合现有治疗方法与CAR-T工程及其临床应用的全部潜力之间的差距。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ace/12354594/518f63138aac/fimmu-16-1581210-g001.jpg

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