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嵌合抗原受体(CAR)细胞衍生外泌体在癌症治疗中的作用:生物发生、工程策略及抗肿瘤机制

CAR Cell-Derived Exosomes in Cancer Therapy: Biogenesis, Engineering Strategies and Antitumor Mechanisms.

作者信息

Si Chaohua, Li Yuanyuan, Wang Yunwen, Gao Jianen, Ma Xu

机构信息

National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100000, China.

出版信息

Int J Mol Sci. 2025 Aug 15;26(16):7890. doi: 10.3390/ijms26167890.

Abstract

Chimeric antigen receptor (CAR) cell therapy, encompassing CAR T, CAR NK, and CAR macrophage cells, demonstrates high efficacy in tumor treatment, conferring durable and effective responses, notably in hematologic malignancies. However, challenges persist in the manufacture of CAR cells, and treatment is associated with serious adverse events, notably cytokine release syndrome (CRS), a potentially life-threatening complication. Owing to the inherent properties of exosomes, CAR cell-derived exosomes offer distinct advantages in cancer therapeutics. CAR cells-derived exosomes retain the inherent tumor-killing function of the parent cells while also exhibiting key practical advantages, including wide availability, safety, and ease of storage and transport. Furthermore, CAR cell-derived exosomes can be combined with other tumor therapies; this combinatorial approach significantly enhances efficacy while reducing side effects. To accelerate the clinical translation of CAR cell-derived exosomes in tumor therapy, this paper reviews their biogenesis, engineering strategies, antitumor mechanisms and clinical evidence, including case studies of combination therapies with other antitumor modalities.

摘要

嵌合抗原受体(CAR)细胞疗法,包括CAR-T、CAR-NK和CAR巨噬细胞,在肿瘤治疗中显示出高效性,能带来持久有效的反应,尤其是在血液系统恶性肿瘤中。然而,CAR细胞的制造仍存在挑战,且治疗会伴随严重不良事件,特别是细胞因子释放综合征(CRS),这是一种潜在的危及生命的并发症。由于外泌体的固有特性,CAR细胞衍生的外泌体在癌症治疗中具有独特优势。CAR细胞衍生的外泌体保留了亲代细胞固有的肿瘤杀伤功能,同时还展现出关键的实际优势,包括广泛可得性、安全性以及易于储存和运输。此外,CAR细胞衍生的外泌体可与其他肿瘤疗法联合使用;这种联合方法能显著提高疗效,同时减少副作用。为加速CAR细胞衍生的外泌体在肿瘤治疗中的临床转化,本文综述了它们的生物发生、工程策略、抗肿瘤机制及临床证据,包括与其他抗肿瘤模式联合治疗的案例研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ece4/12386737/823d9d661147/ijms-26-07890-g001.jpg

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