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干扰素马免疫PET成像,以评估对免疫检查点抑制剂的反应

Justin B Hackett¹, Nicholas Ramos¹, Stephen Barr¹

¹Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States.

Frontiers in oncology

|December 22, 2023

概括

这项研究表明[89Zr]Zr-DFO-anti-IFNγ PET成像可以监测免疫检查点抑制剂 (ICI) 的免疫反应. 在ICI治疗后,IFNγ追踪器有效地检测出瘤中的免疫活性增加,与减少瘤负担相关.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
放射化学放射化学是指辐射化学.

背景情况:

干扰素 (IFNγ) 是免疫反应中的关键细胞因子,特别是在抗瘤免疫和炎症条件中.
免疫检查点抑制剂 (ICI),如抗CTLA-4和抗PD-1,通过调节T细胞活性来增强抗瘤免疫力.
对ICI治疗反应的监测对于优化癌症免疫治疗至关重要.

研究的目的:

调查针对IFNγ ([89Zr]Zr-DFO-anti-IFNγ) 的新型基于89Zr标记的抗体免疫位子发射断层扫描 (immunoPET) 追踪器对ICI的监测反应的实用性.
评估这种追踪器在瘤微环境中检测局部免疫活动的潜力.
评估抗IFNγ抗体追踪器对IFNγ信号传输和ICI疗效的影响.

主要方法:

开发并使用89Zr标记的抗IFNγ抗体追踪器 ([89Zr]Zr-DFO-anti-IFNγ) 用于PET成像.
向携带CT26结直肠瘤的BALB/c小鼠用联合ICI (抗CTLA-4和抗PD-1) 治疗的标记物.
分析了瘤mRNA表达 (qRT-PCR) 对IFNγ信号传递 (IRF1) 的分析,并评估了标记物吸收和瘤负担.

主要成果:

在ICI治疗小鼠中,与对照小鼠相比,观察到[89Zr]Zr-DFO-anti-IFNγ的内摄入量显著增加.
标志物吸收与瘤负担呈反相关性,这表明有效性监测的潜力.
抗IFNγ抗体的标记剂相当剂量并没有降低ICI疗效,而非更高的中和剂量.

结论:

[89Zr]Zr-DFO-anti-IFNγ PET是一种有前途的工具,用于在ICI治疗后非侵入性地监测免疫活性.
这种成像方法可以扩展到其他T细胞激活免疫疗法.
抗IFNγ追踪器可以评估治疗反应而不会影响治疗疗效.

关键词:

免疫检查点抑制剂免疫检查点抑制剂免疫oPET成像成像技术免疫疗法免疫疗法干扰剂干扰剂干扰剂干扰剂放射性跟踪剂是一种放射性跟踪剂.

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