Shamalov Katerina, Meir Rinat, Motiei Menachem, Popovtzer Rachela, Cohen Cyrille J
Laboratory of Tumor Immunology and Immunotherapy, Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
Faculty of Engineering & the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 52900, Israel.
ACS Omega. 2021 Oct 22;6(43):28507-28514. doi: 10.1021/acsomega.1c02143. eCollection 2021 Nov 2.
Natural killer (NK)-cell-based immunotherapy is emerging as an attractive approach for cancer treatment. However, to facilitate and expedite clinical implementation, important questions must be answered regarding the functionality and trafficking patterns of the transferred cells. We have recently developed a noninvasive cell-tracking technique, based on gold nanoparticles (GNPs) as cell-labeling and contrast agents for whole-body computed tomography (CT) imaging. Herein, we report the implementation of this technique for longitudinal and quantitative tracking of NK cell kinetics, the migration and biodistribution in tumor-bearing mice. NK cells were successfully labeled with GNPs, without impairing their biological function, as assessed both , by cytokine release and cytotoxicity assays, and , using a xenograft model of human tumors. Using CT, we longitudinally tracked the migration of intravenously injected NK cells and observed an accumulation of effector cell clusters at the tumor site, up to 72 h. Fluorescence imaging of the cells over time correlated with quantitative analysis of gold content in the tumor, validating the accuracy and reliability of our technique. Our cell-tracking approach thus offers a valuable tool for preclinical studies, as well as for clinical applications, to elucidate the fate of NK cells and promote the implementation of NK-cell-based immunotherapy.
基于自然杀伤（NK）细胞的免疫疗法正成为一种有吸引力的癌症治疗方法。然而，为了促进和加速临床应用，必须回答有关转移细胞的功能和运输模式的重要问题。我们最近开发了一种非侵入性细胞追踪技术，该技术基于金纳米颗粒（GNP）作为细胞标记物和用于全身计算机断层扫描（CT）成像的造影剂。在此，我们报告了该技术在荷瘤小鼠中对NK细胞动力学、迁移和生物分布进行纵向和定量追踪的应用。通过细胞因子释放和细胞毒性试验以及使用人肿瘤异种移植模型评估，NK细胞成功地用GNP标记，且未损害其生物学功能。利用CT，我们纵向追踪了静脉注射的NK细胞的迁移，并观察到效应细胞簇在肿瘤部位的聚集，持续长达72小时。随着时间推移对细胞进行荧光成像与肿瘤中金含量的定量分析相关，验证了我们技术的准确性和可靠性。因此，我们的细胞追踪方法为临床前研究以及临床应用提供了一个有价值的工具，以阐明NK细胞的命运并促进基于NK细胞的免疫疗法的应用。
