In solid tumors, there are multiple barriers for a CAR T cell to surmount in order to reach the tumor site. For better understanding whether CAR T cells effectively infiltrate into tumor site and simultaneously, whether there are off-target effects, real-time monitoring technologies need to be established. Cell-based Positron Emission Tomography (PET) reporter genes have been developed to monitor engineered cells in living subjects. In this study, we reported the construction of a novel reporter gene ΔPSMA pending for monitoring CAR T cells using 68Ga-PSMA-617 a method for tracking the distribution of CAR T cells in vivo was developed. Data were provided to demonstrate that ΔPSMA was predominantly localized on the plasma membrane and could take up 68Ga-PSMA-617 in vitro in a time-dependent manner. And the expression of ΔPSMA did not affect CAR expression and cytolytic capacity of CAR T cells. CAR-ΔPSMA T cell xenografts in nude mice were clearly imaged by PET 60min after injection of 68Ga-PSMA-617. PSMA paired with 68Ga-PSMA-617 was capable of identifying approximately 1×104 engineered CAR T cells. The ability to image small numbers of CAR T cells in vivo would be helpful to accelerate the translation of cell-based therapies into the clinic, and it may reinforce our understanding of treatment success, failure, and toxicity.

中文翻译：

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构建截短的 PSMA 作为 CAR-T 细胞运输的 PET 报告基因。

在实体瘤中，CAR T 细胞需要克服多重障碍才能到达肿瘤部位。为了更好地了解CAR T细胞是否有效同时渗透到肿瘤部位，是否存在脱靶效应，需要建立实时监测技术。基于细胞的正电子发射断层扫描 (PET) 报告基因已被开发用于监测活体受试者中的工程细胞。在这项研究中，我们报道了一种新型报告基因 ΔPSMA 的构建，用于使用 68Ga-PSMA-617 监测 CAR T 细胞，并开​​发了一种跟踪 CAR T 细胞体内分布的方法。提供的数据证明 ΔPSMA 主要位于质膜上，并且可以在体外以时间依赖性方式吸收 68Ga-PSMA-617。并且ΔPSMA的表达不影响CAR表达和CAR T细胞的溶细胞能力。注射 68Ga-PSMA-617 60 分钟后，裸鼠体内的 CAR-ΔPSMA T 细胞异种移植物通过 PET 清晰成像。PSMA 与 68Ga-PSMA-617 配对能够识别大约 1×104 个工程 CAR T 细胞。对少量 CAR T 细胞进行体内成像的能力将有助于加速基于细胞的疗法向临床的转化，并且可能会加强我们对治疗成功、失败和毒性的理解。