dna疫苗
免疫疗法
病毒学
生物
癌症免疫疗法
接种疫苗
佐剂
免疫系统
免疫学
癌症研究
免疫
作者
Xiaoyue Yang,Jiansheng Fan,Yue Wu,Zhiming Ma,Jin Huang,Ying Zhang,Zhan Zhou,Fan Mo,Xuerong Liu,Hong Yuan,Yingchun Xu,Liqiang Pan,Shuqing Chen
标识
DOI:10.1016/j.nano.2021.102443
摘要
Neoantigen-based personalized vaccination has emerged as a viable method for tumor immunotherapy. Here we set up a DNA-based neoantigen vaccine platform with comprehensive identification of individual somatic mutations using whole-exome sequencing (WES) and RNA-seq, bioinformatic prediction of neo-epitopes, dendritic cell (DC)-based efficacy prevalidation of vaccine candidates, optimization of the DNA vaccine and its nanocarrier and adjuvant, and preparation of a liposome-encapsulated multiepitope DNA vaccine. The DNA vaccine was efficiently uptaken by DCs and induced effective immune response against mouse melanoma cells, leading to significant inhibition of melanoma tumor growth and reduction of lung metastasis in a mouse model. Numerous intratumoral infiltrated CD8+ T-cells with specific in vitro killing ability towards melanoma cells were identified. Our study offers evidence that a multiepitope neoantigen DNA vaccine in a nanocarrier can be exploited for personalized tumor immunotherapy and as a reliable prevalidation approach for rapid enrichment of effective neoantigens.
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