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局部辐射通过增加抗原交叉呈现和T细胞透来增强系统CAR T细胞的疗效
Nektarios Kostopoulos1,2,3, Francesca Costabile1,2, Elisavet Krimitza1,2
1Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.
Blood advances
|August 30, 2024
概括
低剂量辐射疗法 (RT) 与仿真抗原受体 (CAR) T细胞疗法相结合,可增强全身抗瘤反应. 这种组合可以通过克服治疗耐药性来改善CD19+淋巴瘤患者的治疗结果.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 辐射瘤学 辐射瘤学
背景情况:
- 化学抗原受体 (CAR) 针对CD19的T细胞治疗 (CART-19) 是对CD19+B细胞淋巴瘤的一种有前途的治疗方法.
- 有相当数量的患者出现复发或对CART-19治疗没有反应.
- 有症状的患者通常需要在CAR T细胞制造过程中进行桥梁放射治疗 (RT).
研究的目的:
- 调查低剂量分成型RT对CART-19治疗反应的影响.
- 探索RT的潜力,作为CAR T细胞治疗的启动和桥梁模式.
主要方法:
- 使用A20淋巴瘤细胞用于CART-19治疗的小鼠模型的开发.
- 低剂量RT的1到2个分数的管理.
- 评估系统性抗瘤反应和瘤在受辐射和非辐射部位的生长.
主要成果:
- 低剂量分成型RT产生了abscopal系统性抗瘤反应.
- 结合RT和CART-19显示了对照射瘤质量的添加效应.
- 在未经辐射的瘤中观察到抗瘤效应的显著增加.
结论:
- 与CART-19疗法相结合的RT显示出增强的抗瘤疗效.
- 机制包括cGAS-STING通路的激活,与瘤相关的抗原交叉启动和表位细胞扩散.
- RT可以作为一种最佳的启动和弥合策略,以改善CD19+血液恶性瘤的结果.
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