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克服当前 CAR-T 疗法困境的新兴策略 - CAR-T 细胞衍生的外泌体。

Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells.

机构信息

School of Basic Medicine and Forensic Medicine, Henan University of Science & Technology, Luoyang, 471023, People's Republic of China.

School of Medical Technology and Engineering, Henan University of Science & Technology, Luoyang, 471023, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Mar 18;19:2773-2791. doi: 10.2147/IJN.S445101. eCollection 2024.

Abstract

Adoptive T cells immunotherapy, specifically chimeric antigen receptor T cells (CAR-T), has shown promising therapeutic efficacy in the treatment of hematologic malignancies. As extensive research on CAR-T therapies has been conducted, various challenges have emerged that significantly hampered their clinical application, including tumor recurrence, CAR-T cell exhaustion, and cytokine release syndrome (CRS). To overcome the hurdles of CAR-T therapy in clinical treatment, cell-free emerging therapies based on exosomes derived from CAR-T cells have been developed as an effective and promising alternative approach. In this review, we present CAR-T cell-based therapies for the treatment of tumors, including the features and benefits of CAR-T therapies, the limitations that exist in this field, and the measures taken to overcome them. Furthermore, we discuss the notable benefits of utilizing exosomes released from CAR-T cells in tumor treatment and anticipate potential issues in clinical trials. Lastly, drawing from previous research on exosomes from CAR-T cells and the characteristics of exosomes, we propose strategies to overcome these restrictions. Additionally, the review discusses the plight in large-scale preparation of exosome and provides potential solutions for future clinical applications.

摘要

过继性 T 细胞免疫疗法,特别是嵌合抗原受体 T 细胞(CAR-T),在治疗血液系统恶性肿瘤方面显示出了有前景的治疗效果。随着对 CAR-T 疗法的广泛研究,出现了许多显著阻碍其临床应用的挑战,包括肿瘤复发、CAR-T 细胞耗竭和细胞因子释放综合征(CRS)。为了克服 CAR-T 疗法在临床治疗中的障碍,基于 CAR-T 细胞衍生的外泌体的无细胞新兴疗法已被开发为一种有效且有前途的替代方法。在这篇综述中,我们介绍了基于 CAR-T 细胞的肿瘤治疗方法,包括 CAR-T 疗法的特点和优势、该领域存在的局限性以及克服这些局限性的措施。此外,我们讨论了利用 CAR-T 细胞释放的外泌体进行肿瘤治疗的显著益处,并预测了临床试验中可能出现的问题。最后,根据 CAR-T 细胞来源的外泌体的先前研究和外泌体的特点,我们提出了克服这些限制的策略。此外,该综述还讨论了大规模制备外泌体的困境,并为未来的临床应用提供了潜在的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b40/10959326/f980b240ceb8/IJN-19-2773-g0001.jpg

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