Zhao Xiaoyan, Zhao Bin, Sun Yan, Liu Aiguo
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, China.
Front Immunol. 2025 Aug 19;16:1655095. doi: 10.3389/fimmu.2025.1655095. eCollection 2025.
Chimeric Antigen Receptor (CAR)-engineered cell therapies excel against hematologic malignancies, however, their efficacy in solid tumors is hampered by toxicity, poor tumor infiltration, immunosuppressive microenvironments, limited persistence, and expansion difficulties. Recently, exosomes derived from CAR-immune cells (CAR-Exosomes) have emerged rapidly as an innovative therapeutic platform. CAR-Exosomes, utilizing nanoscale communication pathways, inherit their parental cells' tumor-targeting capabilities while offering distinct advantage. These advantages encompass low immunogenicity, enhanced tissue penetration, and versatile drug-loading capacity, presenting a promising approach to circumvent the limitations of traditional cell therapies. This review systematically summarizes the core challenges for CAR-T, CAR-NK, and CAR-M cell therapies and emphasizes recent advancements in CAR-Exosomes, including their molecular characteristics, targeted recognition mechanisms, tumor-killing pathways, biosafety, and engineering strategies. Furthermore, it also discusses the key challenges and strategies in the clinical translation of CAR-Exosomes. In conclusion, integrating nanomedicine with cell therapy, CAR-Exosomes hold significant promise as a next-generation platform aiming for high efficacy, safety, and broad clinical applicability in cancer immunotherapy.
嵌合抗原受体(CAR)工程化细胞疗法在治疗血液系统恶性肿瘤方面表现出色,然而,它们在实体瘤中的疗效受到毒性、肿瘤浸润性差、免疫抑制微环境、持久性有限和扩增困难等因素的阻碍。最近,源自CAR免疫细胞的外泌体(CAR-外泌体)作为一种创新的治疗平台迅速兴起。CAR-外泌体利用纳米级通讯途径,继承了其亲代细胞的肿瘤靶向能力,同时具有独特优势。这些优势包括低免疫原性、增强的组织穿透力和多功能的药物装载能力,为克服传统细胞疗法的局限性提供了一种有前景的方法。本综述系统总结了CAR-T、CAR-NK和CAR-M细胞疗法面临的核心挑战,并重点介绍了CAR-外泌体的最新进展,包括其分子特征、靶向识别机制、肿瘤杀伤途径、生物安全性和工程策略。此外,还讨论了CAR-外泌体临床转化中的关键挑战和策略。总之,将纳米医学与细胞疗法相结合,CAR-外泌体作为一个旨在实现癌症免疫治疗高效、安全和广泛临床适用性的下一代平台,具有巨大的潜力。
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