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使用 [18F]四氟硼酸盐正电子发射断层扫描/计算机断层扫描对 CAR-T 细胞进行动态成像

英文原题:Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography.

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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography.

PubMed 2022/02/17(内容时间) J Vis Exp Q3 · IF 1.2(JCR 2025)

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中文摘要

经基因工程改造以表达嵌合抗原受体(CAR)的T细胞在针对B细胞恶性肿瘤或多发性骨髓瘤(MM)患者的关键临床试验中显示出前所未有的结果。然而,由于向肿瘤部位的运输和浸润不良以及在体内缺乏持久性,众多障碍限制了CAR-T 细胞疗法的疗效并阻碍其广泛应用。此外,危及生命的毒性,如细胞因子释放综合征或神经毒性,是主要关注的问题。对CAR-T 细胞进行高效且灵敏的成像和追踪能够评估T细胞的运输、扩增和体内特征,并有助于制定策略以克服CAR-T 细胞疗法当前的局限性。本文描述了在CAR-T 细胞中整合钠碘同向转运体(NIS)以及在临床前模型中使用[18F]四氟硼酸盐-正电子发射断层扫描([18F]TFB-PET)进行CAR-T 细胞成像的方法学。本方案中描述的方法除可用于本研究使用的CAR构建体和靶基因外,还可应用于其他CAR构建体和靶基因。

展开英文摘要原文

T cells genetically engineered to express chimeric antigen receptors (CAR) have shown unprecedented results in pivotal clinical trials for patients with B cell malignancies or multiple myeloma (MM).

However, numerous obstacles limit the efficacy and prohibit the widespread use of CAR T cell therapies due to poor trafficking and infiltration into tumor sites as well as lack of persistence in vivo.

Moreover, life-threatening toxicities, such as cytokine release syndrome or neurotoxicity, are major concerns. Efficient and sensitive imaging and tracking of CAR T cells enables the evaluation of T cell trafficking, expansion, and in vivo characterization and allows the development of strategies to overcome the current limitations of CAR T cell therapy.

This paper describes the methodology for incorporating the sodium iodide symporter (NIS) in CAR T cells and for CAR T cell imaging using [ 18 F]tetrafluoroborate-positron emission tomography ([ 18 F]TFB-PET) in preclinical models. The methods described in this protocol can be applied to other CAR constructs and target genes in addition to the ones used for this study.

论文信息

作者
Sakemura R、Cox MJ、Bansal A、Roman CM、Hefazi M、Vernon CJ、Glynn DL、Pandey MK
第一作者单位
T Cell Engineering, Mayo Clinic; Division of Hematology, Mayo Clinic.
通讯作者单位
T Cell Engineering, Mayo Clinic; Division of Hematology, Mayo Clinic; Department of Molecular Medicine, Mayo Clinic; Department of Immunology, Mayo Clinic; Kenderian.Saad@mayo.edu.
文献类型
非美国政府资助研究 · 音视频资料
期刊
Journal of visualized experiments : JoVE2022 Feb 17
原文标识
PubMed 35253798 · DOI 10.3791/62334