CD73阻断的最佳剂量方案通过ICOS降低调节改善了瘤对放射治疗的反应
Lydia Meziani1,2, Marine Gerbé de Thoré2, Céline Clémenson2
1Laboratory of Radiation Oncology, Department of Radiation Oncology, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland lydia.meziani@chuv.ch eric.deutsch@gustaveroussy.fr.
Journal for immunotherapy of cancer
|June 3, 2023
概括
优化CD73抗体剂量对于增强瘤对联合免疫疗法和放射治疗的反应至关重要. 单剂量在低CD73表达瘤中显示出有效性,而高表达瘤需要多剂量,显示ICOS是关键机制.
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:
- 照射 (IR) 和免疫检查点抑制剂 (ICI) 的联合疗法显示出有前途,但面临治疗耐药性的挑战.
- CD73是一种ectoenzyme,是一种潜在的治疗点,可以提高IR和ICI治疗的疗效.
- 需要对CD73瘤表达水平进行进一步的研究,以指导组合疗法中的CD73向策略.
研究的目的:
- 为了评估不同CD73中和抗体的疗法 (一剂与四剂) 与IR相结合的疗效.
- 评估CD73瘤表达水平对治疗反应的影响.
- 阐明基础机制,包括ICOS在组合治疗中的作用.
主要方法:
- 使用了两种具有明显CD73表达水平 (MC38和TS/A) 的皮下瘤模型.
- 小鼠接受了一剂或四剂抗CD73抗体与IR结合.
- 分析了瘤反应,CD73表达和CD4+T细胞中的ICOS表达.
主要成果:
- TS / A瘤 (高CD73) 响应了四剂抗CD73加IR,而MC38瘤 (低CD73) 没有.
- 一次剂量抗CD73在MC38瘤中显示出显著的抗瘤活性.
- 在MC38细胞中CD73的过度表达需要四剂抗CD73来提高IR疗效.
- 观察到CD4+T细胞iCOS下调和抗CD73加IR治疗的改善反应之间存在相关性.
结论:
- 抗CD73的剂量方案对于改善瘤对IR的反应至关重要.
- iCOS被确定为参与抗CD73疗法的疗效的分子机制.
- 优化免疫疗法-放射疗法组合需要仔细选择剂量策略.
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