肿瘤细胞治疗研究
英文原题：Immunotheranostics in Solid Tumors: Longitudinal Tracking of Human IL13Rα2 CAR-T Cells In Vivo.
CAR-T 细胞疗法在实体瘤治疗中取得的成功有限，这更凸显了阐明这些工程化 T 细胞体内分布的必要性。
嵌合抗原受体（CAR）T细胞疗法治疗实体瘤的成功有限，因此需要阐明工程化T细胞在体内的生物分布。本研究将抗DOTA huC825报告系统（“Thor”平台）整合到新开发的靶向人白细胞介素13受体α2（IL13Rα2）的单链可变片段（scFv）CAR-T细胞中，并在黑色素瘤异种移植小鼠模型中评估其绘制CAR-T细胞分布图的用途。方法：构建表达huC825的抗IL13Rα2 scFv CAR-T细胞（KLG3BBz-huC825），评估检测灵敏度，并每周通过[⁸⁶Y]Y-氨基苄基-DOTA PET/CT监测CAR-T细胞生物分布及治疗效果。结果：KLG3BBz-huC825 T细胞在体外表现出强效抗原特异性细胞毒性和细胞因子释放。Thor放射性半抗原捕获平台的检测灵敏度极高，仅能检测到3,000个工程化T细胞，并可在输注后最长7周持续开展时空动态评估；组织病理学结果对此予以验证。KLG3BBz-huC825治疗带来总生存获益。结论：Thor平台是一种用途广、灵敏度高的方法，可用于研究CAR-T细胞在体内的实时动态。
Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in the treatment of solid tumors, reinforcing the need to elucidate the in vivo biodistribution of these engineered T cells. Here, we integrate the anti-DOTA huC825 reporter ("Thor") platform into newly developed human anti-interleukin-13 receptor -2 (IL13R 2)-single-cell fragment variable (scFv)-derived CAR-T cells and investigate its utility for mapping CAR-T cell distribution in a xenograft mouse model of melanoma. Methods: We engineered anti-IL13R 2-scFv-derived CAR-T cells expressing huC825 (KLG3BBz-huC825), evaluated detection sensitivity, and monitored CAR-T cell biodistribution via weekly [ 86 Y]Y-aminobenzyl-DOTA PET/CT and therapeutic efficacy. Results: KLG3BBz-huC825 T cells demonstrated potent antigen-specific cytotoxicity and cytokine release in vitro. The Thor radiohapten capture platform offered exquisite detection sensitivity of only 3,000 engineered T cells and enabled prolonged spatiotemporal assessment of CAR-T cell kinetics up to 7 wk after infusion, corroborated by histopathology. Treatment with KLG3BBz-huC825 resulted in an overall survival benefit. Conclusion: The Thor platform offers a versatile and highly sensitive approach to study the real-time kinetics of CAR-T cells in vivo.
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