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:Ultrasensitive In Vivo Imaging of Adoptive Immune Cell Distribution and Expansion Using Second Near-Infrared Conjugated Oligoelectrolyte Probes.
监测实体瘤中的过继性细胞治疗对于评估疗效和指导临床用药至关重要,但现有技术灵敏度差、背景信号高且会干扰治疗功能,使监测受到制约。
实体瘤过继细胞治疗的监测对于评估疗效和指导临床用药至关重要,但现有技术存在灵敏度不足、背景信号高和干扰治疗功能等问题。本研究首次将具有第二近红外(NIR-II)荧光的仿生膜共轭低聚电解质COE-BBT用于体内标记和追踪嵌合抗原受体(CAR)工程化NK(CAR-NK)细胞及T(CAR-T)细胞。COE-BBT通过静电和疏水相互作用共同稳定嵌入脂质双层,避免跨膜迁移,并具有信号增强特性,可实现长期标记。优化后的标记方法灵敏度高,在NIR-II成像下,体外可检测约20个标记细胞,体内可检测约50个细胞。在原位和皮下胶质瘤模型中,NIR-II荧光成像可连续追踪CAR-NK和CAR-T细胞的增殖、迁移、肿瘤归巢和穿越血脑屏障,最长可达细胞转移后14天;细胞增殖时荧光信号增强,且不影响细胞活力或细胞毒功能。COE-BBT探针还显示出良好的生物安全性,凸显其作为稳健成像策略的转化潜力,可改进实体瘤过继细胞治疗监测及治疗剂量的临床指导。
Monitoring adoptive cell therapy in solid tumors is critical for evaluating treatment efficacy and guiding clinical medication but is also hindered by poor sensitivity, high background signals, and disruptions of therapeutic functions in existing techniques. In this study, a membrane-mimicking conjugated oligoelectrolyte with second near-infrared (NIR-II) fluorescence, conjugated oligoelectrolytes-benzobisthiadiazole (COE-BBT), is applied for the first time to label and track chimeric antigen receptor (CAR)-engineered natural killer (CAR-NK) cells and T (CAR-T) cells in vivo. COE-BBT stably embeds in lipid bilayers through combined electrostatic and hydrophobic interactions, resists membrane crossing, and supports long-lasting labeling with a lighting-up property. The optimized labeling approach achieves high sensitivity, enabling the detection of as few as ~20 labeled cells in vitro and ~50 cells in vivo under NIR-II imaging. In orthotopic and subcutaneous glioma models, NIR-II fluorescence imaging enables continuous tracking of CAR-NK and CAR-T cell proliferation, migration, tumor homing, and blood-brain barrier penetration for up to 14 d posttransfer as the fluorescence signal is enhanced during proliferation, without compromising cell viability or cytotoxic function. The COE-BBT probe also exhibits favorable biosafety, underscoring its translational potential as a robust imaging strategy to improve solid tumor adoptive cell therapy monitoring and clinical guidance of therapeutic dosing.
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