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 with Chimeric Antigen Receptor T-cell Therapy.
Cardiovascular Toxicities with Chimeric Antigen Receptor T-cell Therapy.
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嵌合抗原受体(CAR)T细胞疗法在治疗儿童和成人高度难治或复发性血液系统恶性肿瘤方面显示出显著疗效。然而,这一有前景的疗法受到严重且可能危及生命的毒性限制。细胞因子释放综合征(CRS)是最常见的毒性之一。CRS的心血管表现包括心动过速、低血压、左心室功能障碍、心律失常、肌钙蛋白升高、心源性休克和肺水肿。近期数据显示,年轻且心脏合并症较少患者的心脏毒性可能短暂且可逆;但对有显著心脏危险因素的老年患者,心脏毒性可能致命。关于CAR-T 相关远期心脏毒性的文献仍有限,监测和预防心脏毒性的共识指南也尚不明确。因此,本综述详细介绍临床试验和观察性研究中CAR-T 治疗的心血管毒性,总结CRS治疗方法,概述当前采用的CAR-T 相关心脏毒性监测方案,并探讨这一迅速发展领域未来的研究方向。
Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in treating highly refractory and relapsing hematological malignancies in pediatric and adult patients.
However, this promising therapy is limited by severe and potentially life-threatening toxicities. Cytokine release syndrome (CRS) is the most commonly observed of these toxicities. The cardiovascular manifestations of CRS include tachycardia, hypotension, left ventricular dysfunction, arrhythmias, troponin elevation, cardiogenic shock, and pulmonary edema.
Recent data suggest that cardiotoxicities may be transient and reversible in younger patients with few cardiac comorbidities; however, cardiotoxicities may be fatal in older patients with significant cardiac risk factors. The literature remains sparse regarding long-term cardiotoxicities associated with CAR-T cell therapy.
Furthermore, consensus guidelines for monitoring and prevention of cardiotoxicities remain illdefined.
Therefore, this review will detail the cardiovascular toxicities of CAR T-cell therapy seen in clinical trials and observational studies, summarize treatment approaches for CRS, outline the currently adopted surveillance protocols for CAR T-cell associated cardiotoxicity, and explore the future directions of research in this rapidly emerging field.
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