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白细胞去除术在 CAR-T 细胞生产和治疗中的应用。

Leukapheresis for CAR-T cell production and therapy.

机构信息

Hematology Department, Athens Medical Center, Athens, Greece.

Hematology Division, Chaim Sheba Medical Center, Israel.

出版信息

Transfus Apher Sci. 2023 Dec;62(6):103828. doi: 10.1016/j.transci.2023.103828. Epub 2023 Oct 11.

Abstract

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-Τ 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.

摘要

嵌合抗原受体 (CAR) T 细胞疗法是一种有效的、个体化的免疫疗法,也是治疗血液系统恶性肿瘤的新方法。目前有 6 种商业 CAR-T 细胞产品获批用于治疗淋巴恶性肿瘤和多发性骨髓瘤。此外,越来越多的临床中心在现场生产 CAR-T 细胞,从而能够现场给药。CAR-T 细胞产品有新鲜的,也有冷冻保存的。制造 CAR-T 细胞是一个复杂的过程,从患者外周血的白细胞分离开始。获得最佳的白细胞分离产品是成功进行 CAR-T 细胞治疗的关键步骤,因此,了解可能影响 T 细胞质量的因素至关重要。用于 CAR-T 细胞生产的白细胞分离术对儿科和成年患者均耐受良好且安全,在许多研究中,CAR-T 细胞治疗呈现出高临床缓解率。CAR-T 细胞疗法正在不断改进,它已经成为临床血液学和干细胞移植设施中自体和异体干细胞移植的标准程序。在患有晚期血液系统恶性肿瘤的患者中,CAR-T 细胞疗法显示出令人难以置信的抗肿瘤疗效。即使在复发或难治性弥漫性大 B 细胞淋巴瘤 (DLBCL) 和急性淋巴细胞白血病 (ALL) 患者中单次输注自体 CD19 靶向 CAR-T 细胞后,也观察到持久缓解,部分患者被治愈。目前正在开发具有更好的 T 细胞持久性和更好的扩增能力的新型构建体。新型下一代 CAR-T 细胞目前被设计用于避免细胞因子释放综合征和神经毒性等毒性。

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