Adoptive cellular therapy (ACT) is a potent strategy to boost the immune response against cancer. ACT is an effective treatment for blood cancers, such as leukemias and lymphomas, but faces challenges treating solid tumors and cancers in locations like the brain. A critical step for success of ACT immunotherapy is achieving efficient trafficking of T cells to solid tumors, and the non-invasive and quantitative tracking of adoptively transferred T cell biodistribution would accelerate its development. Here, we demonstrate the use of Magnetic Particle Imaging (MPI) to non-invasively track ACT T cells in vivo. Labeling T cells with the superparamagnetic iron oxide nanoparticle tracer ferucarbotran did not affect T cell viability, phenotype, or cytotoxic function in vitro. Following ACT, ferucarbotran-labeled T cells were detected and quantified using MPI ex vivo and in vivo, in a mouse model of invasive brain cancer. Proof-of-principle in vivo MPI demonstrated its capacity to detect labeled T cells in lungs and liver after intravenous administration and to monitor T cell localization in the brain after intraventricular administration. Ex vivo imaging using MPI and optical imaging suggests accumulation of systemically administered ferucarbotran-labeled T cells in the brain, where MPI signal from ferucarbotran tracers and fluorescently tagged T cells were observed. Ex vivo imaging also suggest differential accumulation of nanoparticles and viable T cells in other organs like the spleen and liver. These results support the use of MPI to track adoptively transferred T cells and accelerate the development of ACT treatments for brain tumors and other cancers.

中文翻译：

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使用磁性粒子成像跟踪过继性T细胞疗法

过继细胞疗法（ACT）是增强针对癌症的免疫反应的有效策略。ACT是治疗血液癌（例如白血病和淋巴瘤）的有效方法，但在治疗实体瘤和大脑等位置的癌症方面面临挑战。ACT免疫疗法成功的关键步骤是实现T细胞向实体瘤的有效运输，而对过继转移的T细胞生物分布的无创和定量跟踪将加速其发展。在这里，我们展示了磁性粒子成像（MPI）在体内非侵入性追踪ACT T细胞的使用。用超顺磁性氧化铁纳米粒子示踪剂ferucarbotran标记T细胞在体外不影响T细胞的活力，表型或细胞毒性功能。ACT之后，在侵袭性脑癌的小鼠模型中，使用MPI体内和体外检测并标记了Ferucarbotran标记的T细胞。原则上的体内MPI证明了其在静脉内给药后能够检测肺和肝中标记的T细胞并在心室内给药后监测T细胞在大脑中的定位的能力。使用MPI和光学成像的离体成像表明，系统性施用了阿糖胞苷标记的T细胞在大脑中蓄积，在那里观察到了来自阿糖胞苷示踪剂和荧光标记T细胞的MPI信号。离体成像还表明，纳米颗粒和存活的T细胞在脾脏和肝脏等其他器官中的差异蓄积。这些结果支持使用MPI跟踪过继转移的T细胞并加速针对脑肿瘤和其他癌症的ACT治疗的发展。