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:Cardiovascular toxicities associated with novel cellular immune therapies.
Cardiovascular toxicities associated with novel cellular immune therapies.
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过去十年中,T 细胞靶向疗法(包括CAR-T 细胞和双特异性 T 细胞衔接器(BTE)疗法)重塑了越来越多血液系统恶性肿瘤的治疗;近期获批的细胞疗法TIL(肿瘤浸润淋巴细胞)则靶向实体瘤。新兴数据提示,这些疗法可能伴有较高的严重心血管毒性发生率,包括心房颤动、心力衰竭、室性心律失常及其他心血管毒性。这些事件会显著限制治疗后的长期生存。本综述考察当前证据,包括报告的心血管毒性发生率、危险因素、机制及管理策略,重点关注 CAR-T 和 BTE 疗法与心律失常、心力衰竭、心肌炎、出血及其他重大心血管事件的关系。除细胞因子释放综合征与心脏毒性的关联外,本文还描述其他潜在机制,并强调关键未解问题和未来研究方向。
Over the past decade, T-cell-directed therapies, including chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (BTE) therapies, have reshaped the treatment of an expanding number of hematologic malignancies, whereas tumor-infiltrating lymphocytes, a recently approved cellular therapy, targets solid tumor malignancies.
Emerging data suggest that these therapies may be associated with a high incidence of serious cardiovascular toxicities, including atrial fibrillation, heart failure, ventricular arrhythmias, and other cardiovascular toxicities. The development of these events is a major limitation to long-term survival after these treatments. This review examines the current state of evidence, including reported incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities after treatment with these novel therapies.
We specifically focus on CAR-T and BTE therapies and their relation to arrhythmia, heart failure, myocarditis, bleeding, and other major cardiovascular events. Beyond the relationship between cytokine release syndrome and cardiotoxicity, we describe other potential mechanisms and highlight key unanswered questions and future directions of research.
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