在接受CD19 CAR T细胞治疗的白血病患者中,长期反应的免疫代谢决定因素
Lior Goldberg1,2, Eric R Haas3, Jiaqi Wu3
1Department of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratories, Beckman Research Institute, City of Hope, Duarte, CA, USA. lgoldberg@coh.org.
Nature communications
|February 20, 2026
概括
在B细胞急性淋巴细胞白血病 (B-ALL) 中的长期反应CAR T细胞治疗取决于T细胞代谢. 在制造过程中提高T细胞代谢可以改善抗瘤活性和长期缓解.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 在瘤学瘤学.
背景情况:
- 复发性/耐药性B细胞急性淋巴细胞白血病 (B-ALL) 仍然是一个挑战.
- 针对CD19的仿真抗原受体 (CAR) T细胞疗法显示出希望,但由于CAR T细胞功能障碍而面临复发.
- 了解CAR T细胞的免疫代谢对于改善治疗结果至关重要.
研究的目的:
- 调查长期响应者 (LTR) 和短期响应者的CAR T细胞之间的免疫代谢差异.
- 探索骨髓微环境在CAR T细胞功能中的作用.
- 确定增强CAR T细胞抗瘤活性和延长缓解的潜在策略.
主要方法:
- 从B-ALL患者获得的CD19-CAR T细胞的输液前和后综合分析.
- 评估细胞代谢,线粒体功能和关键信号通路 (例如mTOR).
- 在制造过程中体外操纵CAR T细胞代谢.
主要成果:
- 在输注前,来自LTR的CAR T细胞表现出增强的氧化酸化,脂肪酸氧化和酸路径活性.
- LTR CAR T 细胞表现出更高的线粒体质量和更紧的晶状体,具有较低的输注前mTOR表达.
- 在LTR骨髓中的输液后CAR T细胞表现出代谢可塑性和升高的mTOR-pS6信号.
- 在制造过程中暂时抑制mTOR可以改善CAR T细胞代谢重编程和抗瘤功效.
结论:
- 免疫代谢特征可以区分长期响应者和短期响应者在B-ALL CAR T细胞治疗中.
- 骨髓微环境通过代谢可塑性支持CAR T细胞功能.
- 在制造过程中准T细胞代谢是一种有希望的策略,可以增强B-ALL的CAR-T细胞治疗,并提高长期缓解率.
![Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62334.jpg&w=3840&q=50)
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