Pancreatic cancer is a highly aggressive malignancy with relatively low morbidity, which is marked by insidious clinical symptoms but rapid development. The therapeutic options of PC are limited for the insensitivity of traditional chemoradiotherapies. The neoantigen-based vaccine is an emerging tumor immune therapeutic option, but limited evidence proved the efficient therapeutic response in pancreatic cancer.
Whole exome sequencing and bioinformatic analysis as well as quantitative real-time PCR of our previously established human pancreatic cancer cell line were performed to identify neoantigen candidates. The Immunogenicity of prioritized neoantigens was evaluated by analyzing the INF-γ secretion of neoantigen-induced T cell. The antitumor immunity of neoantigen-specific Cytotoxic T cells was examined by the cytotoxicity assay.
The commutative analysis and quantitative real-time PCR identified 13 candidate neoantigens of our previously established human pancreatic cancer cell line PDXPC1 which was confirm as a multi-drug resistant cancer cell line. 4 of 13 candidate neoantigens can be recognized by the immune system and induced strong neoantigen-specific T cell response. The cytotoxic activities mediated by neoantigen-specific T cells significantly inhibited the growth of PDXPC1 tumor cells. Noteworthily, T cells recognized 3 of 4 neoepitopes via the presentation of dendritic cells.
In conclusion, the neoantigens selected by the next generation sequencing and computational algorithm can target the tumor inhibition of pancreatic cancer, which represent a new powerful approach for multidrug resistance and suggest a general strategy for personalized cancer immunotherapy in pancreatic cancer.
The authors.
The Natural Science Foundation of Zhejiang Province.
All authors have declared no conflicts of interest.