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:Second-Generation and Off-the-Shelf CAR Platforms: Emerging Cardiovascular Implications of Next-Generation Cellular Immunotherapies.
Second-Generation and Off-the-Shelf CAR Platforms: Emerging Cardiovascular Implications of Next-Generation Cellular Immunotherapies.
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嵌合抗原受体(CAR)疗法已成为现代癌症治疗的重要组成部分,可为其他治疗难治的血液系统恶性肿瘤患者带来持久缓解。随着其应用的扩展,人们越来越清楚地认识到,这类免疫治疗对心血管系统具有重要影响。CAR相关心血管并发症并非孤立的心肌损伤,而是源于更广泛的炎症过程,其中免疫激活、细胞因子释放、内皮功能障碍和心肌应激密切相关。白细胞介素-6、白细胞介素-1、肿瘤坏死因子-和干扰素-等促炎介质在塑造这些反应中发挥核心作用,尤其是在细胞因子释放综合征期间。从临床角度看,心血管表现常包括低血压、心律失常和左心室功能的短暂下降,在发生高级别炎症毒性的患者中可出现更严重的表现。与此同时,免疫工程学的进展正在改变人们对这些平台的看法,使其意义超越了毒性本身。临床前研究目前提示,基于CAR的方法可能被改造用于调节心脏纤维化并促进心肌修复,这凸显了从纯粹的肿瘤学应用向更广泛的心血管获益转变的潜在可能。将这些进展置于心脏肿瘤学框架中,强调了细致的心血管评估、纵向监测以及专科间密切协作的必要性。
Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded, it has become increasingly clear that these immune-based treatments exert important effects on the cardiovascular system. Rather than reflecting isolated cardiac injury, CAR-associated cardiovascular complications arise from a broader inflammatory process in which immune activation, cytokine release, endothelial dysfunction, and myocardial stress are closely interconnected. Pro-inflammatory mediators such as interleukin-6, interleukin-1 , tumor necrosis factor- , and interferon- play central roles in shaping these responses, particularly during cytokine release syndrome.
From a clinical perspective, cardiovascular manifestations often include hypotension, arrhythmias, and transient reductions in left ventricular function, with more severe presentations occurring in patients who develop high-grade inflammatory toxicity. At the same time, advances in immune engineering are reshaping how these platforms are viewed, extending their relevance beyond toxicity alone.
Preclinical studies now suggest that CAR-based approaches may be adapted to modulate cardiac fibrosis and promote myocardial repair, highlighting a potential shift from purely oncologic applications toward broader cardiovascular benefit. Placing these developments within a cardio-oncology framework emphasizes the need for careful cardiovascular assessment, longitudinal monitoring, and close collaboration between specialties.
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