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CAR-T 免疫治疗中欺骗肿瘤微环境的合成生物学与生物材料策略

英文原题:Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.

查看英文原题

Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.

PubMed 2025/09/01(内容时间) Small Q1 · IF 11.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞免疫疗法已成为癌症治疗中的突破性方法,为多种恶性肿瘤患者带来新希望。然而,由于靶肿瘤同时损伤正常组织的毒性、免疫耐药、T细胞难以浸润肿瘤微环境(TME)以及T细胞耗竭等关键挑战,该疗法治疗实体瘤的成功仍有限。合成生物学和生物材料领域的跨学科创新正在重新定义更智能、反应性更强的CAR-T 细胞工程化方式。近期进展显示,生物材料不仅可用作精准递送载体,还可作为人工抗原呈递细胞(APC)、高通量筛选平台,以及模拟TME复杂生物力学环境的工具。本综述重点介绍这些前沿策略,强调生物材料和合成回路如何支持研究并制定增强CAR-T 细胞实体瘤疗效、同时减少不良反应的策略。文章还展望肿瘤启发型生物材料与T细胞工程交汇领域的未来方向,探讨如何定制新一代CAR-T 疗法以克服TME的重大障碍。

展开英文摘要原文

Chimeric antigen receptor (CAR)-T cell immunotherapy has emerged as a groundbreaking approach in cancer treatment, offering new hope across various malignancies.

However, its success against solid tumors remains limited due to critical challenges, including off-tumor, on-target toxicity, immune resistance, poor T cell infiltration into the tumor microenvironment (TME), and T cell exhaustion. In response, interdisciplinary innovations in synthetic biology and biomaterials are redefining how can be engineer smarter, more responsive CAR-T cells. Recent advances have introduced biomaterials not only as precision delivery vehicles but also as artificial antigen-presenting cells (APCs), high-throughput screening platforms, and tools to replicate the complex biomechanical landscape of the TME.

This review highlights these cutting-edge strategies, emphasizing how biomaterials and synthetic circuits can aid studies and strategies to enhance CAR-T cell efficacy in solid tumors while minimizing adverse effects. Future directions at the intersection of tumor-inspired biomaterials and T cell engineering, envisioning a new generation of CAR-T therapies tailored to overcome the formidable barriers of the TME are also explored.

论文信息

作者
Marsico G、Gc S、Siciliano V
单位
Synthetic and Systems Biology Lab for Biomedicine, Istituto Italiano di Tecnologia-IIT, Largo Barsanti e Matteucci, Naples, 80125, Italy.Italy
文献类型
综述 · 非美国政府资助研究
期刊
Small (Weinheim an der Bergstrasse, Germany)2025 Oct
原文标识
PubMed 40888234 · DOI 10.1002/smll.202506429