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:Myotoxicity in the era of cancer immunotherapy: from mechanisms to multidisciplinary management.
Myotoxicity in the era of cancer immunotherapy: from mechanisms to multidisciplinary management.
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肌毒性,定义为免疫介导的心肌和/或骨骼肌损伤,已成为接受免疫检查点抑制剂(ICI)患者中最严重和致命的免疫相关不良事件(irAE)之一。尽管肿瘤学中的心肌炎并不限于ICI,也可能发生在传统细胞毒性化疗、放疗或选定的靶向治疗后,但ICI相关的心肌毒性以其早发、常与肌炎和重症肌无力重叠以及高病死率而著称。本综述在癌症治疗相关心血管毒性的更广泛背景下概述肌毒性,然后聚焦于与不同免疫治疗类别相关的独特综合征。对于ICI,我们详细描述了包括心肌炎、肌炎和重叠综合征在内的谱系,并通过大型注册研究的数据进行量化。对于嵌合抗原受体(CAR)T细胞治疗,我们聚焦于细胞因子释放综合征(CRS)背景下的心脏毒性。诊断部分讨论了临床表现、生物标志物和影像学,强调需要优先检测肌钙蛋白I而非T,以及对心脏磁共振(CMR)的细致解读。POWER风险评分被提出作为首个外部验证的工具,用于预测ICI引起的早期主要不良心肌毒性事件(MACE)。
最后,本综述提出了针对ICI相关毒性与CAR-T 相关毒性的不同管理策略,并概述了实用的监测方案。
Myotoxicity, defined as immune-mediated injury to cardiac and/or skeletal muscle, has emerged as one of the most severe and lethal immune-related adverse events (irAE) in patients receiving immune checkpoint inhibitors (ICIs). Although myocarditis in oncology is not restricted to ICIs and may also occur after traditional cytotoxic chemotherapy, radiotherapy, or selected targeted therapies, ICI-associated cardiomyotoxicity is distinguished by its early onset, frequent overlap with myositis, and myasthenia gravis, and high case-fatality rate. This review outlines myotoxicity within the broader context of cancer therapy-related cardiovascular toxicity, then focuses on the distinct syndromes associated with different immunotherapy classes.
For ICIs, we detail a spectrum including myocarditis, myositis, and overlap syndromes, quantified by data from large registries. For Chimeric Antigen Receptor (CAR) T-cell therapy, we focus on cardiotoxicity in the context of cytokine release syndrome (CRS).
Diagnostic sections discuss clinical presentation, biomarkers, and imaging, emphasizing the need for troponin I over T and the nuanced interpretation of cardiac magnetic resonance (CMR). The POWER risk score is presented as the first externally validated tool to predict early major adverse cardiomyotoxic events (MACE) from ICIs.
Finally, the review proposes distinct management strategies for ICI- versus CAR-T-related toxicity and outlines pragmatic surveillance protocols.
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