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放射治疗触发的现场瘤疫苗接种通过抗原捕获纳米辅助剂增强检查点阻断的免疫反应

Pei Xu^1,2, Jie Ma², Yang Zhou¹

¹Ningbo Institute of Innovation for Combined Medicine and Engineering, The Affiliated Li Huili Hospital, Ningbo University, Ningbo 315201, China.

|December 22, 2023

概括

这项研究引入了新的纳米辅助剂,可以在放射治疗后捕获瘤抗原,增强局部接种疫苗 (ISV). 将其与免疫检查点封锁相结合,通过逆转T细胞疲劳并诱导铁亡,有效抑制瘤.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
纳米技术纳米技术

背景情况:

在现场接种疫苗 (ISV) 的辅助剂的内注射增强了放射治疗的无效应.
放射治疗诱导的免疫细胞死亡的有限抗原可用性限制了ISV的疗效.

研究的目的:

开发一种战略,最大限度地利用放射治疗诱导的抗原用于增强ISV.
为了研究抗原捕获纳米辅助剂与免疫检查点封锁的协同效应.

主要方法:

开发了载有CpG的Fe3O4纳米颗粒作为纳米辅助剂,用于in situ抗原捕获.
利用点击化学来有效地将抗原与纳米辅助剂结合.
与放射治疗和免疫检查点阻塞相结合的纳米辅助剂在体内.
通过代谢学分析了瘤抑制,T细胞枯竭逆转以及瘤微环境的变化.

主要成果:

纳米辅助剂有效捕获放射治疗诱导的抗原,增加自身抗原和CpG辅助剂的生物可用性.
结合疗法逆转了T细胞枯竭,并显著抑制了治疗和远程瘤.
代谢学揭示了纳米辅助剂破坏了瘤氧化还原平衡,诱导放射治疗后的铁亡.

结论:

抗原捕获纳米辅助剂显示出对抗瘤效应的协同增强的显著潜力.
这一策略有效地克服了放射治疗引起的ISV的抗原限制.
这种方法为改善癌症免疫治疗结果提供了一个有希望的途径.

关键词:

在PD-1封锁中.T细胞耗尽的情况捕获抗原捕获的方法在现场接种疫苗.瘤放射治疗瘤放射治疗

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