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嵌合抗原受体T细胞的毒性及其管理

Toxicity of Chimeric Antigen Receptor T Cells and its Management.

作者信息

Wudhikarn Kitsada, Soh Shui Yen, Huang He, Perales Miguel-Angel

机构信息

Division of Hematology and Research Unit in Translational Hematology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Paediatric Haematology/Oncology Service, KK Women's and Children's Hospital, Singapore.

出版信息

Blood Cell Ther. 2021 Oct 14;4(Spec Edition):S1-S7. doi: 10.31547/bct-2021-011.

Abstract

Recently, chimeric antigen receptor (CAR) T cell therapy has transformed the treatment armamentarium of relapsed/refractory B lymphoid malignancies. CAR T cells provide an excellent response rate and potential cure for these patients. However, CAR T cells also possess unique and potentially life-threatening immune-mediated side effects. Among these, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common complications associated with CAR T cell therapy. While the pathogenesis of CRS involves the activation of complex immune axes, including both cellular networks and inflammatory cytokine milieu, the mechanism of ICANS has not been fully elucidated. Other notable toxicities of CAR T cells include macrophage activation syndrome, cytopenia, and potential organ toxicities. Treatments for these complications typically encompass close observation, multidisciplinary supportive measures, and cytokine-modifying agents such as anti-interleukin-6 antibody and systemic corticosteroids. CAR T therapies can cause immunologic adverse events and management of these toxicities could also instigate a profound immune suppression state that predisposes patients to a variety of infectious complications. Prompt diagnosis and proper management of these complications are crucial to minimize CAR T cell-associated complications and to maximize the outcome of CAR T cell therapy.

摘要

最近,嵌合抗原受体(CAR)T细胞疗法改变了复发/难治性B淋巴细胞恶性肿瘤的治疗手段。CAR T细胞为这些患者提供了出色的缓解率和潜在的治愈机会。然而,CAR T细胞也具有独特的、可能危及生命的免疫介导副作用。其中,细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)是与CAR T细胞疗法相关的两种最常见并发症。虽然CRS的发病机制涉及复杂免疫轴的激活,包括细胞网络和炎性细胞因子环境,但ICANS的机制尚未完全阐明。CAR T细胞的其他显著毒性包括巨噬细胞活化综合征、血细胞减少和潜在的器官毒性。这些并发症的治疗通常包括密切观察、多学科支持措施以及细胞因子调节剂,如抗白细胞介素-6抗体和全身性皮质类固醇。CAR T疗法可引发免疫不良事件,而这些毒性的管理也可能引发严重的免疫抑制状态,使患者易发生各种感染性并发症。对这些并发症进行及时诊断和妥善管理对于将CAR T细胞相关并发症降至最低并使CAR T细胞疗法的疗效最大化至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e39/9847268/a5e86be32e79/2432-7026-4-S-S0001-g001.jpg

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