《生命科学》 2026, 38(4): 607-614
体内CAR-T细胞疗法的研究进展与挑战
摘 要：
嵌合抗原受体T细胞（CAR-T）疗法是肿瘤免疫治疗的革命性技术，其存在体外操作复杂、成本高、治疗周期长等局限性。体内CAR-T细胞疗法作为一种新型的肿瘤免疫疗法，正在成为癌症治疗领域的研究热点。T细胞可以通过递送载体直接在体内诱导产生具有抗肿瘤活性的CAR-T细胞。随着基因递送系统、基因编辑技术和CAR结构的不断优化，体内CAR-T疗法在安全性、有效性和临床转化方面都取得了重大进展。本文回顾了利用载体技术进行体内CAR-T治疗的主要优势以及相关研究进展，并讨论了体内CAR-T疗法面临的挑战，以期为临床应用提供参考。
通讯作者：张 毅 , Email:yizhang@zzu.edu.cn
Abstract:
Chimeric antigen receptor T-cell (CAR-T) immunotherapy has emerged as a revolutionary technology in cancer treatment, demonstrating exceptional efficacy particularly in hematologic malignancies. However, traditional ex vivo CART therapies still face significant limitations, including complex preparation processes, high production costs, lengthy preparation cycles, and the requirement for patients to undergo lymphodepletion pretreatment, which restrict their widespread clinical accessibility. As a highly promising innovative strategy, in vivo CAR-T cell therapy delivers gene drugs directly within the body to reprogram the patient′s own T cells in situ, offering the potential to fundamentally resolve these challenges. This paper comprehensively reviews the latest research advances in in vivo CAR-T therapy, focusing on key technological breakthroughs in the two core delivery platforms: viral and non-viral. Regarding viral vectors, lentivirus (LV) and adeno-associated virus (AAV) are achieving specific targeting of T cells through surface modification techniques to enhance transduction efficiency and reduce off-target risks. In the non-viral vector domain, lipid nanoparticles (LNPs) combined with mRNA technology have garnered significant attention for enabling transient CAR expression, reducing cytokine release syndrome (CRS) risks, and avoiding genomic insertion mutations. Recent clinical trials have demonstrated their potential for treating solid tumors. Additionally, the article highlights the advantages of emerging carriers like polymeric nanoparticles and engineered exosomes in terms of low immunogenicity and controllable delivery. Although in vivo CAR-T therapies have progressed from proof-of-concept to multiple human clinical trials, including platforms like INT2104 and VivoVec, widespread adoption remains hindered by significant challenges. Key obstacles include potential genotoxicity and insertion mutation risks associated with viral vectors, immune escape driven by the complex immunosuppressive microenvironment, dense physical barriers, and antigenic heterogeneity in solid tumors. The article concludes that future research must focus on further optimizing the targeting precision and safety of delivery systems, while integrating gene editing technologies to overcome T-cell exhaustion. This approach will advance in vivo CAR-T therapy into an efficient, universal, and readily available precision treatment solution for tumors.
Communication Author：ZHANG Yi , Email:yizhang@zzu.edu.cn
SciCloud投稿系统