基于菌体的工程疫苗在现场重塑瘤微环境,并引起强大的抗瘤免疫力
Lei Lei1,2, Jiayao Yan1,2, Kai Xin3
1The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008 China.
ACS nano
|May 1, 2024
概括
这项研究引入了一种新的现场疫苗 (ISV),使用工程M13菌体向CD40. 这种方法增强了树突细胞 (DC) 激活,并且在结合癌症免疫疗法中显示出前景.
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:
- 在位疫苗 (ISVs) 利用局部治疗来刺激全身抗瘤免疫力.
- 生物启发的ISV提供免疫辅助作用和遗传适应性.
- 由于其免疫性和可扩展性,M13菌体是癌症疫苗开发的有希望的天然纳米材料.
研究的目的:
- 开发一种基于M13菌体的基因工程ISV,针对CD40进行增强的树突细胞 (DC) 刺激.
- 评估H-GM-M13CD40策略与PD-1阻断结合治疗感冒瘤的疗效.
主要方法:
- 开发了针对CD40 (M13CD40) 的工程M13菌体.
- 免疫性细胞死亡是使用 (S) -10-基托丁 (HCPT) 诱导的.
- 进行了粒细胞-巨细胞殖民地刺激因子 (GM-CSF) 和M13CD40 (H-GM-M13CD40) 的内注射,以招募和激活DCs.
主要成果:
- H-GM-M13CD40策略显著增加了瘤微环境中的DC积累和激活.
- 这种方法逆转了免疫抑制瘤微环境.
- 在冷瘤模型中,H-GM-M13CD40与PD-1阻断的结合表明了协同效应,并诱导了abscopal反应.
结论:
- 工程M13CD40菌体是免疫原的,适合用于癌症疫苗应用.
- 开发的ISV策略有效地刺激DC介导的抗瘤免疫力.
- 这种基于M13菌体的ISV显示出作为癌症免疫疗法的辅助剂的潜力,特别是与检查点封锁相结合.
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