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体内 T 细胞工程:递送策略与临床转化的革命

英文原题:In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.

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In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.

PubMed 2026/03/12(内容时间) BioDrugs Q1 · IF 8.5(JCR 2025)

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中文摘要

涉及嵌合抗原受体(CAR)-T细胞的过继性细胞疗法已被证明是治疗血液系统恶性肿瘤的有效方法,并已成功完成临床转化。传统离体T细胞工程仍受限于耗时长、成本高和可控性差等挑战,而作为一种新兴策略,体内T细胞工程通过多次注射递送载体直接在患者体内生成功能性效应T细胞,可在数天内实现细胞治疗,进一步降低成本并提高可扩展性。本综述按逻辑概述了体内T细胞工程的技术发展与应用,特别关注递送系统的创新,其中我们详细阐述了病毒载体平台和基于RNA的平台的机制及最新进展。此外,我们分析了多种治疗候选物的递送平台及其可用数据,讨论了它们在动物模型和临床应用中的治疗疗效与安全性特征。尽管在实体瘤靶向、精准调控和生产方面仍存在一些挑战,但越来越多的临床前和临床数据已揭示,体内编程策略在广泛疾病谱中具有巨大的治疗潜力。

展开英文摘要原文

Adoptive cell therapies involving chimeric antigen receptor (CAR)-T cells have been demonstrated to be efficient treatments for hematologic malignancies and have successfully completed clinical translation. While traditional ex vivo T-cell engineering is still limited by challenges such as time-consuming processes, high costs, and poor controllability, as an emerging strategy, in vivo T-cell engineering involves the generation of functional effector T cells directly within patients through several injections of delivery vectors, which can reach cell therapies in days, further reducing costs and increasing scalability.

This review logically outlines the technical development and application of in vivo T-cell engineering, with a particular focus on innovations in delivery systems, in which we elaborate on the mechanism and latest advances in viral vector platforms and RNA-based platforms.

Furthermore, we analyzed the delivery platforms of multiple therapeutic candidates and their available data, discussing their therapeutic efficacy and safety profiles in both animal models and clinical applications. Although some challenges remain in solid tumor targeting, precise regulation, and manufacturing, increasing preclinical and clinical data have revealed the immense therapeutic potential of in vivo programming strategies across a broad spectrum of diseases.

论文信息

作者
Dong X、Yan W、Long X、Wu M
第一作者单位
The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Central South University, Changsha, 410013, Hunan, China.China
通讯作者单位
The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Central South University, Changsha, 410013, Hunan, China. wuminghua554@aliyun.com.China
文献类型
综述
期刊
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2026 May
原文标识
PubMed 41817927 · DOI 10.1007/s40259-026-00771-3