开发一种基于抗原的方法,实时无创性地成像 CAR T 细胞,并将其作为一种预测工具。

Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.

机构信息

David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

出版信息

Sci Adv. 2024 Sep 20;10(38):eadn3816. doi: 10.1126/sciadv.adn3816. Epub 2024 Sep 18.

Abstract

CAR T cell therapy has revolutionized the treatment of a spectrum of blood-related malignancies. However, treatment responses vary among cancer types and patients. Accurate monitoring of CAR T cell dynamics is crucial for understanding and evaluating treatment efficacy. Positron emission tomography (PET) offers a comprehensive view of CAR T cell homing, especially in critical organs such as lymphoid structures and bone marrow. This information will help assess treatment response and predict relapse risk. Current PET imaging methods for CAR T require genetic modifications, limiting clinical use. To overcome this, we developed an antigen-based imaging approach enabling whole-body CAR T cell imaging. The probe detects CAR T cells in vivo without affecting their function. In an immunocompetent B cell leukemia model, CAR-PET signal in the spleen predicted early mortality risk. The antigen-based CAR-PET approach allows assessment of CAR T therapy responses without altering established clinical protocols. It seamlessly integrates with FDA-approved and future CAR T cell generations, facilitating broader clinical application.

摘要

嵌合抗原受体 T 细胞(CAR T)疗法已经彻底改变了一系列血液相关恶性肿瘤的治疗方法。然而,癌症类型和患者的治疗反应存在差异。准确监测 CAR T 细胞动力学对于理解和评估治疗效果至关重要。正电子发射断层扫描(PET)提供了对 CAR T 细胞归巢的全面观察,特别是在淋巴结构和骨髓等关键器官中。这些信息将有助于评估治疗反应和预测复发风险。目前用于 CAR T 的 PET 成像方法需要基因修饰,限制了其临床应用。为了克服这一限制,我们开发了一种基于抗原的成像方法,实现了全身 CAR T 细胞成像。该探针可以在不影响其功能的情况下在体内检测 CAR T 细胞。在免疫功能正常的 B 细胞白血病模型中,脾脏中的 CAR-PET 信号预测了早期死亡风险。基于抗原的 CAR-PET 方法可以在不改变既定临床方案的情况下评估 CAR T 治疗反应。它与 FDA 批准的和未来的 CAR T 细胞代际无缝集成,促进了更广泛的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31a5/11409975/b3feaf9dcb38/sciadv.adn3816-f1.jpg

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