肿瘤细胞治疗研究
英文原题:Biomaterial Techniques for Enhancing CAR-T Cell Therapy of Solid Tumours.
Biomaterial Techniques for Enhancing CAR-T Cell Therapy of Solid Tumours.
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生物材料赋能的方法提供了一套多功能工具,用以解决限制 CAR-T 细胞治疗实体瘤的关键生物学和转化障碍。基于临床熟悉材料和简化设计的策略似乎最适合近期临床转化,强调需要在工程创新与安全性、可扩展性以及融入现有临床工作流程之间取得平衡。
嵌合抗原受体(CAR)-T细胞疗法在血液系统恶性肿瘤中已取得显著临床成功,但在实体瘤中疗效有限。关键障碍包括肿瘤转运不足、免疫抑制性肿瘤微环境、抗原选择性和表达异质性差,以及安全性和生产制造相关的挑战。基于生物材料的技术已成为应对其中许多局限性的潜在策略。本综述旨在批判性评估旨在增强CAR-T 细胞治疗实体瘤的生物材料方法,并评估其转化潜力。
对近期临床前转化研究进行了叙述性综述,重点关注为提高 CAR-T 细胞在实体瘤环境中的递送、持久性、功能性、安全控制和制造效率而开发的生物材料平台。根据其作用机制、治疗获益和转化准备阶段对这些方法进行了分析。
生物材料策略,包括纳米颗粒、可注射和可植入水凝胶、支架及混合递送系统,已在多种实体瘤模型中改善了 CAR-T 的浸润、存活和治疗疗效。细胞因子和其他免疫调节信号的局部递送实现了对 CAR-T 激活更好的时空控制,降低了全身毒性,并提高了持久性。其他应用包括放大 ex vivo CAR-T 扩增以及支持非病毒或 in vivo CAR-T 生成。然而,材料复杂性的增加往往伴随着可扩展性、监管审批和长期安全性方面的挑战。
A narrative review of recent pre-clinical translational studies was conducted, focussing on biomaterial platforms developed to improve CAR-T cell delivery, persistence, functionality, safety control, and manufacturing efficiency in solid-tumour settings. Approaches were analysed according to their mechanisms of action, therapeutic benefits, and stage of translational readiness.
Biomaterial strategies, including nanoparticles, injectable and implantable hydrogels, scaffolds, and hybrid delivery systems, have improved CAR-T infiltration, survival, and therapeutic efficacy in several solid-tumour models. Localised delivery of cytokines and other immunomodulatory cues enabled improved spatio-temporal control of CAR-T activation, reducing systemic toxicity, and increasing persistence. Additional applications include amplified ex vivo CAR-T expansion and support for non-viral or in vivo CAR-T generation. However, increased material complexity was frequently associated with challenges in scalability, regulatory approval, and long-term safety.
Biomaterial-enabled approaches offer a versatile toolkit to address key biological and translational barriers limiting CAR-T cell therapy of solid tumours. Strategies based on clinically familiar materials and simplified designs appear most suitable for near-term clinical translation, emphasising the need to balance engineering innovation with safety, scalability, and integration into existing clinical workflows.
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