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用于 CAR-T 细胞制备和治疗的白细胞分离术

英文原题:Leukapheresis for CAR-T cell production and therapy.

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Leukapheresis for CAR-T cell production and therapy.

PubMed 2023/10/11(内容时间) Transfus Apher Sci Q4 · IF 1.2(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法是一种有效的个体化免疫疗法,也是血液系统恶性肿瘤的新型治疗方法。目前已有六种商业CAR-T 产品获批用于淋巴系统恶性肿瘤和多发性骨髓瘤。

此外,越来越多的临床中心开始现场生产CAR-T 细胞,使患者可在院内接受治疗。CAR-T 产品既可新鲜输注,也可冷冻保存。CAR-T 细胞制备流程复杂,始于白细胞单采以获取患者外周血T细胞。优化单采产品是CAR-T 治疗成功的关键,因此必须了解可能影响T细胞质量的因素。儿童和成人患者均能良好耐受CAR-T 制备所需的白细胞单采,且CAR-T 疗法在多项研究中获得较高临床缓解率。CAR-T 疗法不断改进,已逐步成为提供自体和异基因移植的临床血液学及干细胞移植中心近乎常规的治疗流程。对晚期血液系统恶性肿瘤患者,CAR-T 显示出卓越抗肿瘤疗效;复发/难治性弥漫性大B细胞淋巴瘤(DLBCL)和急性淋巴细胞白血病(ALL)患者即使仅接受一次自体CD19 CAR-T 输注,也可获得持久缓解,部分患者甚至治愈。未来将开发持续性和扩增能力更强的新型构建体;新一代CAR-T 目前正被设计用于避免细胞因子释放综合征和神经毒性等不良反应。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy is an effective, individualized immunotherapy, and novel treatment for hematologic malignancies. Six commercial CAR-T cell products are currently approved for lymphatic malignancies and multiple myeloma.

In addition, an increasing number of clinical centres produce CAR-T cells on-site, which enable the administration of CAR-T cells on site. The CAR-T cell products are either fresh or cryopreserved. Manufacturing CAR-T cells is a complicated process that begins with leukapheresis to obtain T cells from the patient's peripheral blood. An optimal leukapheresis product is crucial step for a successful CAR-T cell therapy; therefore, it is imperative to understand the factors that may affect the quality or T cells. The leukapheresis for CAR-T cell production is well tolerated and safe for both paediatric and adult patients and CAR- cell therapy presents high clinical response rate in many studies.

CAR-T cell therapy is under continuous improvement, and it has transformed into an almost standard procedure in clinical haematology and stem cell transplantation facilities that provide both autologous and allogeneic stem cell transplantations. In patients suffering from advanced haematological malignancies, CAR-T cell therapy shows incredible antitumor efficacy.

Even after a single infusion of autologous CD19-targeting CAR-T cells in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) and acute lymphoblastic leukaemia (ALL), long lasting remission is observed, and a fraction of the patients are being cured. Future novel constructs are being developed with better T cell persistence and better expansion. New next-generation CAR-T cells are currently designed to avoid toxicities such as cytokine release syndrome and neurotoxicity.

论文信息

作者
Pessach I、Nagler A
第一作者单位
Hematology Department, Athens Medical Center, Athens, Greece.Greece
通讯作者单位
Hematology Division, Chaim Sheba Medical Center, Israel. Electronic address: a.nagler@sheba.health.gov.il.Israel
文献类型
综述
期刊
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis2023 Dec
原文标识
PubMed 37838564 · DOI 10.1016/j.transci.2023.103828