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开发基于抗原的 CAR-T 细胞实时无创成像方法及其作为预测工具的应用

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

查看英文原题

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

PubMed 2024/09/18(内容时间) Sci Adv Q1 · IF 13.9(JCR 2025)

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中文摘要

CAR-T 细胞疗法已经彻底改变了多种血液相关恶性肿瘤的治疗。然而,治疗反应因癌症类型和患者而异。准确监测 CAR-T 细胞动态对于理解和评估治疗疗效至关重要。正电子发射断层扫描(PET)可全面观察 CAR-T 细胞的归巢,尤其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并预测复发风险。当前用于 CAR-T 的 PET 成像方法需要基因修饰,限制了临床应用。为克服这一限制,我们开发了一种基于抗原的成像方法,能够实现全身 CAR-T 细胞成像。该探针可在体内检测 CAR-T 细胞,而不影响其功能。在免疫健全的 B 细胞白血病模型中,脾脏中的 CAR-PET 信号可预测早期死亡风险。基于抗原的 CAR-PET 方法可在不改变既定临床方案的情况下评估 CAR-T 治疗反应。它可无缝整合到 FDA 批准的和未来的 CAR-T 细胞世代中,促进更广泛的临床应用。

展开英文摘要原文

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.

论文信息

作者
Fröse J、Rowley J、Farid AS、Rakhshandehroo T、Leclerc P、Mak H、Allen H、Moravej H
第一作者单位
David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.United Kingdom
通讯作者单位
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Science advances2024 Sep 20
原文标识
PubMed 39292778 · DOI 10.1126/sciadv.adn3816