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嵌合抗原受体 T 细胞(CAR-T)疗法在临床实践中的障碍。

Barriers to Chimeric Antigen Receptor T-Cell (CAR-T) Therapies in Clinical Practice.

机构信息

Cardinal Health, Dublin, OH, USA.

Hematology Oncology Associates of CNY, Syracuse, NY, USA.

出版信息

Pharmaceut Med. 2022 Jun;36(3):163-171. doi: 10.1007/s40290-022-00428-w. Epub 2022 Jun 7.

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy is a revolutionary cancer treatment modality where a patient's own T cells are collected and engineered ex vivo to express a chimeric antigen receptor (CAR). These reprogrammed CAR-T cells, when reinfused into the same patient, stimulate a T-cell mediated immune response against the antigen-expressing malignant cells leading to cell death. The initial results from pivotal clinical trials of CAR-T agents have been promising, leading to multiple approvals in various hematologic malignancies in the relapsed setting, including acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, follicular lymphoma, and, more recently, multiple myeloma. However, since the initial trials and US Food and Drug Administration approvals, there have been significant barriers to the widespread use of this therapy. The barriers to the use of CAR-T therapy include complex logistics, manufacturing limitations, toxicity concerns, and financial burden. This review discusses potential solutions to overcome these barriers in order to make this life-changing therapy widely accessible.

摘要

嵌合抗原受体 T 细胞(CAR-T)疗法是一种革命性的癌症治疗方法,在此方法中,患者自身的 T 细胞被采集并在体外进行工程改造,以表达嵌合抗原受体(CAR)。这些重编程的 CAR-T 细胞在重新输注到同一患者体内时,会刺激针对表达抗原的恶性细胞的 T 细胞介导的免疫反应,导致细胞死亡。CAR-T 药物的关键性临床试验的初步结果令人鼓舞,导致在复发环境下的多种血液恶性肿瘤中获得了多个批准,包括急性淋巴细胞白血病(ALL)、弥漫性大 B 细胞淋巴瘤(DLBCL)、套细胞淋巴瘤、滤泡性淋巴瘤,以及最近的多发性骨髓瘤。然而,自最初的试验和美国食品和药物管理局(FDA)批准以来,这种疗法的广泛应用存在着重大障碍。CAR-T 疗法的使用障碍包括复杂的物流、制造限制、毒性问题和经济负担。这篇综述讨论了克服这些障碍的潜在解决方案,以便使这种改变生活的疗法广泛普及。

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