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为了有效的CAIX向放射性核素和检查点抑制组合治疗先进的清晰细胞脏细胞癌

Simone C Kleinendorst¹, Egbert Oosterwijk², Janneke Molkenboer-Kuenen¹

¹Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

|July 1, 2024

概括

将向放射性核素疗法 (TRT) 与免疫检查点抑制剂 (ICI) 结合起来,对晚期清细胞细胞癌 (ccRCC) 显示出有前途. 在临床前模型中,低剂量[177Lu]Lu-DOTA-hG250 TRT加上ICI显著改善了结局,并改变了瘤微环境.

科学领域:

在瘤学瘤学.
核医学就是核医学.
免疫治疗是一种免疫疗法.

背景情况:

先进的清晰细胞细胞癌 (ccRCC) 对免疫检查点抑制剂 (ICI) 的反应有限.
放射治疗可以增强抗瘤免疫力,提高ICI的疗效.
向放射性核素疗法 (TRT) 提供了一种系统方法,用于精确照射转移性癌症.

研究的目的:

调查结合[177Lu]Lu-DOTA-hG250 TRT的潜力,向碳酸无水酶IX (CAIX),与ICI用于ccRCC治疗.
在临床前模型中评估这种联合治疗的治疗和免疫效应.

主要方法:

在携带Renca-CAIX或CT26-CAIX瘤的小鼠中评估了[177Lu]Lu-DOTA-hG250的生物分布.
通过监测瘤生长和存活率来评估带有和没有ICI的TRT疗效.
使用免疫组织化学,流细胞计和RNA分析分析了瘤微环境的变化.

主要成果:

[177Lu]Lu-DOTA-hG250在两种模型中都显示出高瘤吸收率.
亚治疗性[177Lu]Lu-DOTA-hG250 (4 MBq) 与aPD-1+aCTLA-4或a-PD1的组合导致显著的抗瘤疗效和完全缓解.
组合治疗诱导了DNA损伤,增加了T细胞透,并在瘤微环境中调节了免疫信号.

结论:

亚治疗性[177Lu]Lu-DOTA-hG250与ICI结合,在ccRCC模型中显示出优异的治疗结果.
这种组合疗法显著改变了瘤微环境,这表明在先进的ccRCC中具有临床应用的潜力.
需要进一步的研究,以优化这种组合治疗在临床环境中的应用.

关键词:

癌症治疗方法癌症治疗方法综合模式治疗疗法综合模式治疗免疫检查点抑制剂免疫检查点抑制剂有针对性的放射性核酸治疗瘤微环境瘤微环境

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