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加强基于ESC的TAA癌症疫苗的免疫反应,使用一种新的OMV传递系统

Meiling Jin¹, Da Huo¹, Jingjing Sun¹

¹Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Chinese Academy of Sciences, Shenzhen, China.

Journal of nanobiotechnology

|January 3, 2024

概括

工程化细菌外膜囊泡 (OMVs) 提供胚胎干细胞 (ESC) 衍生的瘤抗原和PD-L1抗体,增强CD8+ T细胞反应并减少小鼠的瘤生长.

科学领域:

免疫学免疫学免疫学
生物技术是生物技术.
在瘤学瘤学.

背景情况:

胚胎干细胞 (ESC) 衍生的表位表现为癌症疫苗有前途,但患有免疫性差和CD8+ T细胞反应弱.
细菌外膜囊泡 (OMV) 是有效的免疫辅助剂和瘤抗原的传递载体.

研究的目的:

开发一个工程OMV平台,用于联合输送ESC衍生的瘤抗原 (TAA) 和PD-L1抗体,以增强抗瘤免疫力.
通过增强T细胞反应和增加抗原停留时间来提高基于ESC的癌症疫苗的疗效.

主要方法:

通过将SpyCatcher (SpC) 和Staphylococcal Protein A (SpA) 融合到OmpA.通过工程设计的细菌外膜囊泡 (OMVs).
开发了一个使用SpyTag-peptide和SPA-抗体相互作用的OMV与ESC衍生的TAA和抗PD-L1抗体的结合系统.
在小鼠瘤模型中评估了基于OMV的组合疗法的治疗疗效.

主要成果:

设计的OMV与TAA和PD-L1抗体有效结合,增加TAA的停留时间.
组合疗法显著抑制了小鼠的瘤生长.
治疗增强了IFN-γ产生CD8+ T细胞的反应,增加了CD8+记忆细胞,并增强了抗原特异性T细胞.

结论:

新的OMV平台使得ESC衍生的TAA和免疫检查点抑制剂能够有效地同时提供.
这种基于OMV的输送系统增强了抗瘤免疫反应,并有可能开发有效的癌症疫苗.

关键词:

胚胎干细胞是一种胚胎干细胞.剧情片 (Epitopes) 是一种表情片.机器人驾驶汽车 (OMV) 的使用瘤免疫系统的免疫力疫苗疫苗是一种疫苗.

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