肿瘤细胞治疗研究
英文原题：Development of an in situ CAR-T cell protocol through optical and PSMA-targeted PET imaging.
原位T细胞转染方法克服了传统嵌合抗原受体（CAR）-T疗法相关的复杂性和高成本。
体内T细胞转染方法可克服传统嵌合抗原受体（CAR）T细胞疗法复杂且成本高昂的问题。然而，体内CAR-T策略作用于患者复杂的免疫环境，并绕过输注前的体外细胞质量控制，因此需要先进成像技术追踪免疫细胞迁移和功能。正电子发射断层显像（PET）可检测患者体内生化过程；若结合工程化细胞特异性放射性示踪剂，则可监测CAR-T细胞转运。本研究开发了一种体内生成、追踪和功能评估T细胞的方法：使用抗CD5偶联脂质纳米颗粒共同递送CD19 CAR mRNA（mCAR19）和前列腺特异性膜抗原mRNA（mPSMA）标记。在IL-7预处理和重复给药条件下，该方法使75%的B细胞淋巴瘤荷瘤小鼠无肿瘤生存，疗效与体外制备方法相近；通过68Ga-PSMA-617 PET成像，进一步验证体内工程化、带PSMA标记的CD19 CAR-T细胞生成及其肿瘤浸润。
In situ T cell transfection methods overcome the complexity and high costs associated with conventional chimeric antigen receptor (CAR)-T therapy. However, the in situ CAR-T cell approach operates within the patient's complex immune environment and bypasses preinfusion ex vivo cellular quality controls, necessitating advanced imaging techniques to track immune cell migration and function. Positron emission tomography (PET) can detect biochemical processes in patients and, when combined with a radiotracer specific for the engineered cells, can monitor CAR-T cell trafficking. Herein, we develop an approach for in situ T cell generation, tracking, and functional assessment using anti-CD5-conjugated lipid nanoparticles for codelivering CD19 CAR mRNA (mCAR19) and a prostate-specific membrane antigen mRNA (mPSMA) tag. With interleukin-7 (IL-7) preconditioning and repeated administration, this approach achieves tumor-free survival in 75% of B cell lymphoma-bearing mice (similar efficacy to ex vivo approaches), and through PET imaging of 68 Ga-PSMA-617, the generation and tumor infiltration of in situ-engineered PSMA-tagged CD19 CAR-T cells is validated.
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