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用 immunoPET 评估小鼠对内免疫疗法的局部和远程反应

Louis Meyblum^1,2, Céline Chevaleyre¹, Sandrine Susini^3,4

¹Université Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France.

Journal for immunotherapy of cancer

|November 10, 2023

概括

免疫检查点阻断剂 (ICBs) 的内注射减少了全身暴露,同时保持了疗效. 免疫PET成像显示,ICB有效治疗注射和远程瘤,支持临床应用.

科学领域:

免疫治疗是一种免疫疗法.
放射性药物成像技术放射性药物成像技术
药理动力学药理动力学

背景情况:

免疫检查点阻断剂 (ICB) 是有前途的,但面临着瘤耐药性和不良事件等挑战.
内免疫治疗的目的是减少副作用并提高局部药物度.
了解ICB分布和在内分娩后对远程瘤的影响至关重要.

研究的目的:

通过使用immunoPET成像来研究放射性标记的抗CTLA-4抗体在内与静脉注射后的分布.
在注射和非注射瘤中评估内ICB输送的疗效.
为了评估瘤内ICBs对瘤微环境的影响.

主要方法:

在小鼠中建立了同源性结直肠瘤模型 (CT26和MC38).
标有-89的抗CTLA-4抗体 ([89Zr]9H10) 被输入内或静脉.
通过免疫PET成像监测全身分布;评估瘤反应和微环境变化.

主要成果:

内注射导致药物持续存在于注射瘤中 (6-8%的7天的ID).
不注射ICB的瘤吸收在内和静脉注射之间是可比的.
在长期ICB暴露的CT26瘤中观察到完整的瘤反应和增加的CD8+T细胞.

结论:

免疫PET成像支持内ICB输送,以减少全身暴露并保持疗效.
在注射的瘤中,内口ICB可以实现高局部药物水平和显著的治疗效果,而非注射瘤.
这种immunoPET方法可以指导临床实践和基于证据的癌症免疫治疗药物开发.

关键词:

在CTLA-4抗原.药物评估,临床前临床免疫检查点抑制剂免疫检查点抑制剂瘤生物标志物瘤生物标志物

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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.