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瘤微环境响应纳米免疫调节器用于增强化学抗原受体-T细胞疗法在肺癌

Qian Chen^1,2, Jie Sun³, Sisi Ling¹

¹CAS Key Laboratory of Nano-Bio Interface, Suzhou Key Laboratory of Functional Molecular Imaging Technology, Division of Nanobiomedicine and i-Lab, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.

|February 24, 2025

概括

这项研究引入了一种新型纳米药物,通过重新编程瘤微环境来增强固体瘤的CAR-T细胞疗法. 这种纳米药物改善了CAR-T细胞透和瘤杀伤效率,为癌症免疫治疗提供了一个有前途的策略.

科学领域:

免疫学免疫学免疫学
纳米技术纳米技术
在瘤学瘤学.

背景情况:

化学抗原受体 (CAR) -T细胞疗法在血液癌症中显示出高疗效.
用CAR-T细胞治疗固体瘤受到免疫抑制瘤微环境 (TME) 的阻碍.

研究的目的:

开发一种对TME敏感的纳米免疫调节器 (FMANAC),以增强对固体瘤的CAR-T细胞免疫疗法.
为了重建免疫化学基因梯度并克服TME介导的CAR-T细胞活性抑制.

主要方法:

FMANAC是使用多组件协调自组装合成的.
这种纳米药物释放C-C化学连体5 (CCL5) 和NLG919作为对酸性TME的反应.
该策略在H460肺癌动物模型中使用CD276CAR-T细胞和近红外II光成像进行了评估.

主要成果:

在酸性TME中FMANAC的分解引发了药物释放,恢复了化学激素梯度,并增强了CAR-T细胞透.
NLG919逆转了因多胺2,3-二氧化酶 (IDO) 介导的免疫抑制,为CAR-T细胞创造了有利的环境.
结合的纳米调节策略在肺癌模型中显著提高了瘤治疗疗效.

结论:

响应TME的纳米免疫调节器 (FMANAC) 有效地克服了固体瘤诱导的免疫抑制.
这种纳米调节方法与CAR-T细胞疗法和先进的成像学相结合,为增强癌症免疫疗法提供了一个强有力的策略.

关键词:

在CAR-T细胞中.在 NIR-II 光成像中使用 NIR-II 光成像.免疫疗法免疫疗法肺癌是一种肺癌.瘤微环境是一个微环境.

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