决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Circadian rhythm-guided cellular therapy in hematologic malignancies: mechanisms, clinical evidence, and optimization strategies.
昼夜节律是内源性 24 小时计时系统,通过中枢和外周时钟协调造血和免疫功能。
昼夜节律是内源性24小时计时系统,通过中枢和外周生物钟协调造血及免疫功能。越来越多证据表明,血液系统恶性肿瘤的发生和进展常伴昼夜节律紊乱;节律紊乱不仅参与恶性转化和疾病进展,还会影响抗肿瘤免疫及治疗应答差异。细胞疗法,尤其是造血干细胞移植(HSCT)和CAR-T 细胞疗法(CAR-T),已成为治疗血液系统恶性肿瘤的重要手段,并显示出显著临床疗效,但其结局和毒性受到昼夜节律调控的显著影响。本综述总结血液系统恶性肿瘤中的昼夜节律机制,以及HSCT和CAR-T的时间治疗证据,并讨论相关机会,包括按时间安排细胞采集、制造、输注及治疗后护理。我们还强调,个体化昼夜节律相位评估可作为制定个性化治疗时序的基础。总体而言,将昼夜节律原则纳入血液系统细胞治疗,有望改善植入、增强抗肿瘤疗效、降低毒性,并为更精准和个体化的治疗提供切实可行的框架。
Circadian rhythms are endogenous 24-hour timing systems that coordinate hematopoiesis and immune function through central and peripheral clocks. Increasing evidence indicates that the initiation and progression of hematologic malignancies are frequently accompanied by circadian disruption, which not only contributes to malignant transformation and disease progression but also anti-tumor immunity and variable treatment responses. Cellular therapies, particularly hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T), have emerged as transformative modalities for hematologic malignancies, demonstrating remarkable clinical efficacy. However, their outcomes and toxicities are significantly influenced by circadian regulation. This review summarizes circadian mechanisms in hematologic malignancies and chronotherapy evidence for HSCT and CAR-T. And we discuss chronotherapeutic opportunities, including timed cell collection, manufacturing, infusion, and post-treatment care. We further highlight the clinical relevance of individualized circadian phase assessment as a foundation for personalized treatment scheduling. Collectively, integrating circadian principles into hematologic cellular therapy may improve engraftment, enhance antitumor efficacy, reduce toxicity, and provide a practical framework for more precise and personalized treatment.
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