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:In vivo tracking of CAR-T cells in tumors via nanobubble-based contrast enhanced ultrasound.
我们基于超声的追踪方法能够有效监测 CAR-T 细胞在体内的迁移,提供了一种有价值的新策略,可进一步推动新型 CAR-T 产品的开发以及调控细胞迁移的策略。
CAR-T细胞疗法显著改善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结局。鉴于其在血液系统恶性肿瘤中的成功,研究者正广泛致力于开发CAR-T疗法治疗实体瘤。实体瘤治疗的一大难点在于细胞运输和迁移,二者对达到疗效并减少肿瘤外不良反应至关重要。开发简单、安全且低成本的临床体内CAR-T细胞分布追踪方法,可为改进实体瘤CAR-T产品提供关键认识。本文展示一种策略:使用纳米气泡(NB)标记细胞,并通过超声成像在体内监测CAR-T细胞。NB是一种超声造影剂,由脂质外壳和C₄F₁₀气体核心组成,可被细胞高效摄取。该方法利用非线性对比增强超声(CEUS)成像CAR-T细胞。研究发现,CAR-T细胞注入荷瘤和非荷瘤小鼠体内后均可被成像观察。总之,这种基于超声的追踪方法可有效监测CAR-T细胞体内迁移,为促进新型CAR-T产品开发及细胞迁移调控策略提供了有价值的新途径。
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 to treat solid tumors. The treatment of solid tumors poses significant hurdles with cell trafficking necessary to achieve efficacy and minimize off-tumor side effects. The development of simple, safe and inexpensive modalities for tracking CAR-T cell distribution in clinical use in vivo 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 of 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.
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