CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Mathematical models and computational approaches in CAR-T therapeutics.
Mathematical models and computational approaches in CAR-T therapeutics.
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我们提出了一个综合框架,利用这些模型推进 CAR-T 细胞疗法,弥合现有治疗方法与 CAR-T 工程及其临床应用全部潜力之间的差距。
合成生物学旨在工程化改造活体生物,以实现特定治疗用途。CAR-T 因具备灵活性、特异性、可预测性和可控性,已成为癌症治疗的突破性方法。CAR-T 通过基因改造 T 细胞以靶向肿瘤特异性抗原。然而,现有模型在时空分辨率方面不足,限制了疗法的安全性、成本效益和总体潜力,实体瘤治疗尤为如此。主体内容:本文探讨数学模型和计算技术如何改进 CAR-T 设计并预测治疗结局,重点关注抗原受体功能、治疗效力和潜在不良反应等关键因素。作者考察 CAR-T 细胞动力学及抗原结合的影响,并讨论克服抗原逃逸、CRS 和复发的策略。
作者提出利用这些模型推进 CAR-T 疗法的综合框架,以弥合现有治疗方法与 CAR-T 工程及其临床应用全部潜力之间的差距。
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.
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.
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