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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography.
Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography.
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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。
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.
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