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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team.
Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team.
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免疫介导毒性的发生是 CAR-T 治疗常见的挑战。决定这种毒性的机制仍不清楚,尽管不利的肿瘤微环境和促炎状态使患者处于风险之中。CAR-T 后毒性的监测、诊断和治疗必须根据国际指南和内部临床实践来确定。迫切需要识别能够识别出发生并发症风险更大的患者的生物标志物。采用一致的分级标准是持续改进毒性管理策略的必要条件。一线治疗包括支持性护理和托珠单抗或皮质类固醇治疗。早期启动细胞因子阻断治疗可以减轻毒性。该计划将包括细胞因子释放预防、风险适应性治疗、预防 on-target/off-tumor 效应以及 CAR-T 开关方法。
嵌合抗原受体(CAR)-T细胞疗法是一种用于其他治疗失败的血液系统恶性肿瘤患者的新疗法。涵盖领域:本综述概述了识别和管理与CAR-T 细胞相关的最急性毒性反应。
INTRODUCTION: Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed. AREAS COVERED: The review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells. EXPERT OPINION: The development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk.
The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually.
The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.
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