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Yonghyun Lee^1,2,3,4, Jongyoon Shinn^5,6, Cheng Xu^7,8

¹Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul, 03760, South Korea. y.lee@ewha.ac.kr.

Nature communications

|August 8, 2023

概括

这项研究开发了向纳米颗粒 (SC144@HABN) 来诱导免疫细胞死亡 (ICD) 和重新编程免疫抑制瘤相关髓状细胞 (TAMCs). 这种组合疗法显示出克服对癌症免疫疗法的耐药性的前景.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
纳米医学是一种纳米医学.

背景情况:

瘤相关髓状细胞 (TAMCs) 创造了一个免疫抑制的瘤微环境,阻碍了癌症免疫治疗的有效性.
诱导免疫细胞死亡 (ICD) 是增强抗瘤免疫力的策略,但其与TAMC调节的结合仍然具有挑战性.
IL-6/gp130/STAT3信号通路与TAMC介导的免疫抑制有关.

研究的目的:

开发一种针对gp130抑制剂 (SC144) 的向药物递送系统,同时诱导ICD和调节TAMCs.
评估SC144装载纳米粒子 (SC144@HABN) 与免疫检查点阻塞 (ICB) 结合的疗效.

主要方法:

氨酸 - 氨酸纳米颗粒 (HABN) 的开发,以向CD44hi瘤细胞和TAMC.
在体外和体内评估SC144@HABN对瘤细胞ICD,巨细胞两极分化和免疫细胞群的影响.
在MC38和4T1瘤模型中使用SC144@HABN和抗PD-L1ICB的组合疗法研究.

主要成果:

SC144@HABN成功诱导了瘤细胞亡和ICD,并使巨细胞偏向M1类表型.
在SC144@HABN治疗下降了免疫抑制的髓衍生抑制细胞和调节性T细胞,同时促进了抗瘤CD8+T细胞.
使用SC144@HABN和抗PD-L1ICB的组合疗法在敏感和耐药模型中显著消除了瘤.

结论:

通过HABN对SC144的向输送提供了诱导ICD和克服TAMC介导免疫抑制的双重策略.
这种组合化疗免疫疗法方法显示出治疗具有挑战性的癌症,包括ICB耐药瘤的巨大潜力.
开发的纳米医学平台突出了促进癌症免疫治疗策略的有希望的途径.

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