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智能 CAR-T 纳米共生体:原型与初始模型

英文原题:Smart CAR-T Nanosymbionts: archetypes and proto-models.

查看英文原题

Smart CAR-T Nanosymbionts: archetypes and proto-models.

PubMed 2025/08/12(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

个体化医疗通过使治疗方案匹配每位患者独特的生物学特征,重新定义了癌症治疗。CAR-T 细胞疗法是一个典型例子:该疗法对患者自身T细胞进行基因改造,使其识别并杀伤癌细胞。CAR-T 在血液系统恶性肿瘤中取得显著疗效,并开始在实体瘤和自身免疫性疾病中显示潜力。但其进一步普及受到多重挑战限制,包括制备复杂、成本高、实体瘤疗效有限,以及潜在的严重毒性。纳米技术为克服许多障碍提供了新可能。工程化纳米颗粒可改善基因递送、更精准地靶向肿瘤、增强免疫细胞功能,并实现体内CAR-T 生成,减少劳动密集型的体外制备流程。

然而,尽管前景可期,纳米技术向临床转化仍面临监管障碍、规模化困难,以及人体模型中重复性不一致等问题。与此同时,人工智能(AI)凭借强大的数据分析和预测建模算法,正在改变先进疗法的设计、评估和监测方式,包括优化制备流程。对于CAR-T,AI有望改善患者分层、提高治疗应答和毒性预测能力,并加快、更精确地设计CAR构建体及递送系统。本综述结合这三大技术支柱,提出“Smart CAR-T Nanosymbionts”整合框架,由AI指导纳米技术增强型CAR-T 疗法的设计与部署。

我们探讨这类融合如何优化用于mRNA转染的脂质纳米颗粒制剂、实现肿瘤的特异性靶向并改造肿瘤微环境、实时监测CAR-T 细胞行为和毒性、改善体内CAR-T 生成,以及克服实体瘤治疗障碍。

最后,本文也讨论活细胞疗法与计算驱动系统这一新兴交叉领域的伦理和监管问题。“Smart CAR-T Nanosymbionts”框架(图1)代表一项变革性进展,有望推动个体化癌症治疗更加精准、可及且有效。

展开英文摘要原文

Personalized medicine has redefined cancer treatment by aligning therapies with each patient's unique biological profile. A key example is chimeric antigen receptor T-cell (CAR-T) therapy, in which a patient's own T cells are genetically modified to recognize and destroy cancer cells. This approach has delivered remarkable results in hematologic malignancies and is beginning to show promise in solid tumors and autoimmune diseases.

However, its broader adoption is limited by major challenges, including complex manufacturing, high costs, limited efficacy in solid tumors, and potentially severe toxicities. Nanotechnology offers exciting possibilities to overcome many of these barriers. Engineered nanoparticles can improve gene delivery, target tumors more precisely, enhance immune cell function, and enable in vivo CAR-T production, reducing the need for labor-intensive ex vivo processes.

However, despite this promise, translation into clinical settings remains difficult due to regulatory hurdles, scalability issues, and inconsistent reproducibility in human models. At the same time, artificial intelligence (AI), with its powerful algorithms for data analysis and predictive modeling, is transforming how we design, evaluate, and monitor advanced therapies, including the optimization of manufacturing processes.

In the context of CAR-T, AI holds strong potential for better patient stratification, improved prediction of treatment response and toxicity, and faster, more precise design of CAR constructs and delivery systems. Leveraging these three technological pillars, this review introduces the concept of Smart CART Nanosymbionts , an integrated framework in which AI guides the design and deployment of nanotechnology-enhanced CAR-T therapies.

We explore how this convergence enables optimization of lipid nanoparticle formulations for mRNA transfection, specific targeting and modification of the tumor microenvironment, real-time monitoring of CAR-T cell behavior and toxicity, and improved in vivo CAR-T generation and overcoming barriers in solid tumors.

Finally, it's important we also address the ethical and regulatory considerations surrounding this emerging interface of living therapies and computational driven systems. The Smart CART Nanosymbionts framework ( Figure 1 :) represents a transformative step forward, promising to advance personalized cancer treatment toward greater precision, accessibility, and overall effectiveness.

论文信息

作者
Baena JC、Victoria JS、Toro-Pedroza A、Aragón CC、Ortiz-Guzman J、Garcia-Robledo JE、Torres D、Rios-Serna LJ
第一作者单位
Division of Oncology, Department of Medicine, Fundación Valle del Lili, ICESI University, Cali, Colombia.
通讯作者单位
Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.United Kingdom
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 40873579 · DOI 10.3389/fimmu.2025.1635159