CAR-T治疗后细胞因子释放综合征的发生机制与临床治疗
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摘要
靶向CD19的嵌合抗原受体修饰T细胞(CAR-T)疗法在B细胞肿瘤治疗中取了重大进展,美国FDA已批准了2项CD19 CAR-T治疗产品上市。随着CAR-T、双特异性T细胞衔接器(BiTE)和双重高亲靶向蛋白(DART)以及基因修饰的T细胞受体疗法(TCR-T)等免疫治疗临床及机制研究的开展,其潜在风险及副作用得到更广泛的认识,尤其是细胞因子释放综合征(CRS)。CRS是目前CAR-T治疗后最常见的并发症,重者可能危及生命。CRS病理生理学机制复杂,涉及多种免疫细胞及非免疫细胞,并可累及全身各脏器,研究CRS发生发展机制对提高CAR-T治疗安全性有重要意义。近年来,研究者们在动物模型中对CRS机制进行了更深入的研究。本文论述CRS的发生、病理生理学机制、动物模型、临床特征以及分级治疗等研究进展,旨在为更深入地从机制层面了解CRS,更安全地开展CAR-T临床应用提供指导。
Chimeric antigen receptor T-cell(CAR-T) targeting CD19 has made significant progress in the treatment of B cell malignancies. FDA has approved two CD19 CAR-T therapeutic products. With the development in the clinical and mechanism research of immunotherapy(CAR-T, bispecific T-cell engager [BiTE]), dual affinity re-targeting [DART], and genetically modified T cell receptor T cell [TCR-T]), its potential risks and side effects have been more widely recognized, especially cytokine release syndrome(CRS).CRS is currently the most common complication after CAR-T treatment and can be life-threatening in severe cases. Moreover, the pathophysiological process of CRS is complex, involving a variety of immune cells and non-immune cells, and can affect whole body organs. Elucidating the mechanisms of CRS development is of great significance to improve the safety of CAR-T therapy. In recent years, researchers have conducted study in animal models to illustrate the mechanisms of CRS more deeply. This review discusses the development, pathophysiological mechanisms, animal models, clinical features, and graded treatments of CRS, aiming to provide an in-depth understanding of the mechanism of CRS and improve the safety of CAR-T therapy.
Chimeric antigen receptor T-cell(CAR-T) targeting CD19 has made significant progress in the treatment of B cell malignancies. FDA has approved two CD19 CAR-T therapeutic products. With the development in the clinical and mechanism research of immunotherapy(CAR-T, bispecific T-cell engager [BiTE]), dual affinity re-targeting [DART], and genetically modified T cell receptor T cell [TCR-T]), its potential risks and side effects have been more widely recognized, especially cytokine release syndrome(CRS).CRS is currently the most common complication after CAR-T treatment and can be life-threatening in severe cases. Moreover, the pathophysiological process of CRS is complex, involving a variety of immune cells and non-immune cells, and can affect whole body organs. Elucidating the mechanisms of CRS development is of great significance to improve the safety of CAR-T therapy. In recent years, researchers have conducted study in animal models to illustrate the mechanisms of CRS more deeply. This review discusses the development, pathophysiological mechanisms, animal models, clinical features, and graded treatments of CRS, aiming to provide an in-depth understanding of the mechanism of CRS and improve the safety of CAR-T therapy.
引文
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