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低剂量向放射性核素治疗与CAR T细胞协同作用,增强瘤反应
Yanping Yang1,2, Yogindra Vedvyas1,2, Yago Alcaina2
1Department of Radiology, Houston Methodist Research Institute, Houston, TX, United States.
Frontiers in immunology
|March 29, 2024
概括
结合化学抗原受体 (CAR) T细胞疗法与向放射性核素疗法 (TRT) 的结合显示出有前途. 低剂量的TRT增强了CAR T细胞疗法,导致瘤回归和细胞因子增加,而高剂量则有害.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 辐射疗法 辐射疗法
背景情况:
- 电离辐射正在探索免疫疗法协同作用.
- 化学抗原受体 (CAR) T细胞疗法在癌症治疗中显示出潜力.
- 向放射性核酸治疗 (TRT) 提供局部辐射输送.
研究的目的:
- 为了研究使用177Lu-DOTATATE的CAR T细胞治疗和TRT的组合.
- 确定TRT的最佳剂量和时间,以增强抗瘤免疫力.
- 评估TRT对CAR T细胞透,扩张和疗效的影响.
主要方法:
- 经过工程设计,可以产生表达索马托斯塔丁受体2 (SSTR2) 的CAR T细胞.
- 177Lu-DOTATATE通过CAR T细胞传递到瘤中.
- 使用18F-NOTA-Octreotide追踪CAR T细胞动态的正子发射断层扫描 (PET).
- 在TRT给药后,对瘤反应和细胞因子水平进行了监测.
主要成果:
- 低剂量TRT (2.5 Gy) 与CAR T细胞结合导致瘤迅速回归,并增加了促炎细胞因子.
- 更高的TRT剂量 (6 Gy) 也减少了瘤负担,但导致瘤和CAR T细胞的显著细胞死亡.
- 存在一种潜在的最佳TRT剂量范围,用于增强T细胞活性和瘤细胞敏感化.
结论:
- 将CAR T细胞治疗与TRT结合起来是可行的,可以增强抗瘤免疫力.
- TRT剂量至关重要;最佳范围可以最大限度地提高治疗效益,同时最大限度地降低毒性.
- 这种方法有望在癌症治疗中实现更持久的瘤控制.
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