Synthetic multiepitope neoantigen DNA vaccine for personalized cancer immunotherapy
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-e...
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Veröffentlicht in: | Nanomedicine 2021-10, Vol.37, p.102443-102443, Article 102443 |
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Sprache: | eng |
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Zusammenfassung: | 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.
Generation of synthetic multiepitope neoantigen DNA vaccine. Somatic mutations were identified by WES and further confirmed by RNA-seq. Each mutation sequence was cloned into the pVAX1 vector and transfected into BMDCs. Transfected BMDCS could stimulate naive T-cells to specifically kill mouse melanoma B16F10 cells. Potent mutations were selected and combined in a tandem mini-gene (TMG), followed by encapsulation with CpG-armed liposome for treatment of the melanoma mouse model. [Display omitted] |
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ISSN: | 1549-9634 1549-9642 |
DOI: | 10.1016/j.nano.2021.102443 |