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基于嵌合抗原受体(CAR)疗法的最新进展:体内CAR生成作为细胞癌症治疗的一场革命。

State of the art in CAR-based therapy: In vivo CAR production as a revolution in cell-based cancer treatment.

作者信息

Esmaeilzadeh Abdolreza, Hadiloo Kaveh, Yaghoubi Sara, Makoui Masoud Hassanzadeh, Mostanadi Parsa

机构信息

Pficell R&D Canadian Institution & Corporation, Profound Future Focused Innovative Cell and Gene Therapy, Pficell Canadian Institution and Corporation, Ontario, Canada.

Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran.

出版信息

Cell Oncol (Dordr). 2025 Apr 22. doi: 10.1007/s13402-025-01056-7.

Abstract

Chimeric antigen receptor (CAR) therapy has successfully treated relapsed/refractory hematological cancers. This strategy can effectively target tumor cells. However, despite positive outcomes in clinical applications, challenges remain to overcome. These hurdles pertain to the production of the drugs, solid tumor resistance, and side effects related to the treatment. Some cases have been missed during the drug preparation due to manufacturing issues, prolonged production times, and high costs. These challenges mainly arise from the in vitro manufacturing process, so reevaluating this process could minimize the number of missed patients. The immune cells are traditionally collected and sent to the laboratory; after several steps, the cells are modified to express the CAR gene before being injected back into the patient's body. During the in vivo method, the CAR gene is introduced to the immune cells inside the body. This allows for treatment to begin sooner, avoiding potential failures in drug preparation and the associated high costs. In this review, we will elaborate on the production and treatment process using in vivo CAR, examine the benefits and challenges of this approach, and ultimately present the available solutions for incorporating this treatment into clinical practice.

摘要

嵌合抗原受体(CAR)疗法已成功治疗复发/难治性血液系统癌症。该策略可有效靶向肿瘤细胞。然而,尽管在临床应用中取得了积极成果,但仍有挑战有待克服。这些障碍涉及药物生产、实体瘤耐药性以及与治疗相关的副作用。由于制造问题、生产时间延长和成本高昂,在药物制备过程中出现了一些病例遗漏。这些挑战主要源于体外制造过程,因此重新评估这一过程可减少遗漏患者的数量。传统上,免疫细胞被采集并送往实验室;经过几个步骤后,细胞被修饰以表达CAR基因,然后再注入患者体内。在体内方法中,CAR基因被引入体内的免疫细胞。这使得治疗能够更快开始,避免药物制备过程中的潜在失败以及相关的高成本。在本综述中,我们将详细阐述使用体内CAR的生产和治疗过程,研究这种方法的益处和挑战,并最终提出将这种治疗纳入临床实践的可用解决方案。

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