中文摘要
CAR-T 细胞疗法已在急性淋巴细胞白血病 (ALL)、B 细胞淋巴瘤和多发性骨髓瘤患者的结局方面取得了显著进展。鉴于这些在血液系统恶性肿瘤中的成功,目前大量研究集中于开发用于治疗实体瘤的 CAR-T 细胞疗法。实体瘤的治疗面临着重大障碍,需要细胞 trafficking 才能实现疗效并尽量减少脱靶副作用。开发简单、安全且廉价的模式来追踪 CAR-T 细胞在人体内的分布,可以提供关键见解,以促进改进的实体瘤 CAR-T 产品的开发。
在此,我们展示了一种利用超声成像和纳米气泡 (NB) 标记细胞在体内监测 CAR-T 细胞的策略。NB 是由脂质壳和 C 4 F 10 气体核心组成的超声造影剂,可以有效地内化到细胞中。这种方法使我们能够使用非线性对比增强超声 (CEUS) 对 CAR-T 细胞进行成像。利用这种方法,我们发现 CAR-T 细胞在注射到荷瘤小鼠和非荷瘤小鼠后均可被可视化。
总之,我们基于超声的追踪方法可以有效地监测 CAR-T 细胞在体内的 trafficking,提供了一种有价值的新策略,可以进一步促进新 CAR-T 产品的开发以及调节细胞 trafficking 的策略。
展开英文摘要原文
CAR-T cell therapy has led to remarkable advances in the outcomes of patients with acute lymphoblastic leukemia (ALL), B cell lymphomas, and multiple myeloma. Given these successes in hematologic malignancies, extensive efforts are now focused on developing CAR-T cell therapies for the treatment of solid tumors.
The treatment of solid tumors poses significant hurdles with cell trafficking that is necessary to achieve efficacy and minimize off-tumor side effects. The development of simple, safe and inexpensive modalities to track CAR-T cell distribution in humans could provide critical insights to facilitate the development of improved CAR-T products for solid tumors.
Here we demonstrate a strategy to monitor CAR-T cells in vivo using ultrasound imaging and nanobubble (NB) labeled cells. NBs are ultrasound contrast agents composed of a lipid shell and a C 4 F 10 gas core that can be efficiently internalized into cells. This approach enables us to image the CAR-T cells using nonlinear contrast-enhanced ultrasound (CEUS).
Utilizing this method, we found that CAR-T cells can be visualized after injection into both tumor bearing and non-tumor bearing mice. In summary, our ultrasound-based tracking approach can effectively monitor the trafficking of CAR-T cells in vivo , offering a valuable new strategy that can further enable the development of new CAR-T products and strategies to modulate cell trafficking.
论文信息
- 作者
- Durig D、Franklin J、Perera R、Jackson Z、Vasanna H、Kolios MC、Wald D、Exner AA
- 文献类型
- 预印本
- 期刊
- bioRxiv : the preprint server for biology2025 May 10