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:Noninvasive in vivo tracking of SPIONs-labeled CLDN18.2-targeted CAR-T cells in gastric cancer via magnetic particle imaging.
Noninvasive in vivo tracking of SPIONs-labeled CLDN18.2-targeted CAR-T cells in gastric cancer via magnetic particle imaging.
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本研究拟采用磁粒子成像(MPI)对 CLDN18.2 特异性 CAR-T 细胞进行体内追踪并定量评估其靶向能力。输注前,CLDN18.2 靶向 CAR-T 细胞用超顺磁性氧化铁纳米颗粒(SPION)标记以进行 MPI,并用近红外荧光染料 DiR 标记以进行荧光分子成像(FMI)。将标记或未标记 CAR-T 细胞静脉注射至携带 HGC27 异种移植瘤的 NOD/SCID 小鼠,可单独给药或与抗 PD-L1(aPD-L1)抗体联用(成像组 n = 3,治疗组 n = 5)。FMI 和 MPI 成功监测 CAR-T 细胞动态迁移并靶向 CLDN18.2 过表达肿瘤。输注后第 5 天,肿瘤中 SPION 标记 CAR-T 细胞的 MPI 信号显著高于标记的正常 T 细胞。MPI 联合 FMI 成功监测了 CAR-T 细胞对胃癌的 CLDN18.2 特异性靶向,为评估 CAR-T 联合 aPD-L1 免疫治疗提供了潜在框架。
This study aims to employ magnetic particle imaging (MPI) for in vivo tracking and quantitative assessment of targeting capability of CLDN18. 2-specific CAR-T cells. CLDN18. 2-targeted CAR-T cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic particle imaging (MPI), and with the near-infrared fluorescent dye DiR for fluorescence molecular imaging (FMI) before infusion. SPIONs-labeled and unlabeled CAR-T cells were administered intravenously to NOD/SCID mice bearing HGC27 xenograft tumors, either independently or in combination with anti-PD-L1 (aPD-L1) antibody (n = 3 for imaging and n = 5 for treatment).
The FMI and MPI successfully monitored the dynamic migration and tumor targeting of CAR-T cells towards CLDN18. 2-overexpressing tumors. On the fifth day post-infusion, the MPI signal of SPIONs-labeled CAR-T cells was significantly higher in the tumor than that of labeled normal T cells. MPI combined with FMI successfully monitored the targeting of CLDN18. 2-specific CAR-T cells in gastric cancer, providing a potential framework for evaluating CAR-T therapy combined with aPD-L1 immunotherapy.
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