CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review.
Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review.
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T 细胞衔接器(TCE)是一类癌症免疫疗法,近期已显示可使血液系统恶性肿瘤和实体瘤患者获益。TCE 预计将广泛使用,这带来实施挑战,也凸显了提前预防、减轻和管理不良事件的指南需求。TCE 可将 T 细胞直接募集至肿瘤细胞接触位置,引发必然且即时的抗肿瘤免疫应答,可能导致多种反应和不良事件。细胞因子释放综合征(CRS)是最常见反应,主要发生于递增给药的首次用药阶段。应根据临床症状、发生时间、病理生理特征和临床管理方式,将 CRS 与输注相关反应区分。TCE 其他常见反应和不良事件包括免疫效应细胞相关神经毒性综合征(ICANS)、感染、肿瘤炎症反应和血细胞减少。本综述总结 TCE 和 CAR-T 毒性谱的相似点和差异。与 CAR-T 相比,TCE 导致严重 CRS 或 ICANS 的频率较低。本文回顾 TCE 相关反应和不良事件的术语、病理生理机制、严重程度分级系统及管理方法。
T-cell engagers (TCE) are cancer immunotherapies that have recently demonstrated meaningful benefit for patients with hematological malignancies and solid tumors. The anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events. By mobilizing T-cells directly at the contact of tumor cells, TCE mount an obligatory and immediate anti-tumor immune response that could result in diverse reactions and adverse events. Cytokine release syndrome (CRS) is the most common reaction and is largely confined to the first drug administrations during step-up dosage.
Cytokine release syndrome should be distinguished from infusion related reaction by clinical symptoms, timing to occurrence, pathophysiological aspects, and clinical management. Other common reactions and adverse events with TCE are immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), infections, tumor flare reaction and cytopenias.
The toxicity profiles of TCE and CAR-T cells have commonalities and distinctions that we sum-up in this review. As compared with CAR-T cells, TCE are responsible for less frequently severe CRS or ICANS. This review recapitulates terminology, pathophysiology, severity grading system and management of reactions and adverse events related to TCE.
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