《生命科学》 2026, 38(4): 689-701

体内CAR-T载体递送技术的研究现状与展望

于 阔^1,2 , 王振坤^1,3,*

¹哈尔滨医科大学，国家卫生健康委员会细胞移植重点实验室，哈尔滨 150000 ²东北农业大学生命科学学院，黑龙江省动物细胞与遗传工程重点实验室，哈尔滨 150030 ³哈尔滨医科大学附属第一医院中心实验室，哈尔滨 150000

摘　要：

体内原位生成嵌合抗原受体T细胞（chimeric antigen receptor T cell，CAR-T）疗法作为一种新兴的治疗策略，在实现标准化产品制备、降低治疗成本以及缩短治疗周期方面展现出巨大潜力。本文聚焦于体内CAR-T治疗的关键技术——载体递送系统，深入探讨了不同递送载体的作用机制及其优劣势，综述了该领域的最新研究进展与面临的技术挑战，旨在为优化体内CAR-T治疗策略及推动其临床转化提供理论参考。

通讯作者：王振坤 , Email:zhenkunwang@hrbmu.edu.cn

Research progress and future perspectives on in vivo CAR-T vector delivery technology

YU Kuo^1,2 , WANG Zhen-Kun^1,3,*

¹NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin 150000, China ²Heilongjiang Provincial Key Laboratory of Animal Cell and Genetic Engineering, College of Life Sciences, Northeast Agricultural University, Harbin 150030, China ³Central Laboratory, First Affiliated Hospital, Harbin Medical University, Harbin 150000, China

Abstract:

In vivo chimeric antigen receptor T-cell (CAR-T) therapy is an emerging paradigm that enables direct genetic engineering of T cells within patients, bypassing ex vivo manufacturing. This approach addresses key limitations of traditional CAR-T therapy, including lengthy production time, high costs, T-cell exhaustion, and integration-related mutagenesis risks, while promising standardized, accessible, and safer treatments. This review systematically evaluates vector delivery systems essential for in vivo CAR-T generation. Viral vectors, including lentiviral (LVs) and adeno-associated viral (AAVs) vectors,
leverage natural transduction mechanisms. Engineered LVs with retargeted envelopes achieve efficient, durable CAR expression via genomic integration. AAVs offer lower immunogenicity and primarily episomal persistence, enhanced by serotype optimization and capsid engineering for improved T-cell specificity and reduced pre-existing immunity. Non-viral vectors, led by lipid nanoparticles (LNPs), provide scalable production, flexible cargo capacity (mRNA/DNA/CRISPR), and proven safety from mRNA vaccine applications. Challenges like hepatic tropism are mitigated through lipid formulation tuning, surface ligand conjugation, and alternative dosing routes. Emerging biomimetic nanoparticles, such as cell membrane coated or fusogenic virus-like particles, enhance biocompatibility, immune evasion, and targeted cytosolic delivery. Key challenges include viral integration/immunogenicity risks, non-viral transient expression and endosomal escape, off-target effects, and solid tumor microenvironment barriers. Solutions encompass multi-domain ligands, transposon integration, codelivery of immunomodulators, and stimulus-responsive designs. Comparative analysis reveals application-specific suitability: LVs for hematologic malignancies needing long-term surveillance; LNPs for autoimmune diseases via transient ″immune reset″; biomimetics for superior evasion. Phase I trials of viral platforms show promising safety and efficacy. Future success hinges on enhancing delivery precision, balancing expression durability with safety, and standardizing production. Multidisciplinary advances will expand in vivo CAR-T beyond oncology to autoimmune disorders, transplant tolerance, and chronic infections, heralding accessible precision immunotherapy. 

Communication Author：WANG Zhen-Kun , Email:zhenkunwang@hrbmu.edu.cn