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Anti-tumour effect of neo-antigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

Authors :
Wenfeng Li
Huan Qin
Qiang Li
Feilong Wang
Kun Wang
Zhang Jing
Yanan He
Jiaxing Sun
Zhang Wei
Haiyan Hu
Ximing Liao
Xiaoping Su
Qi Yin
Source :
Journal of Cancer Research and Clinical Oncology
Publication Year :
2021
Publisher :
Springer Science and Business Media LLC, 2021.

Abstract

Purpose Mutation-specific T-cell response to epithelial cancers and T-cell-based immunotherapy has been successfully used to treat several human solid cancers. We aimed to investigate the anti-tumour effect of neo-antigen-reactive T(NRT) cells induced by RNA mutanome vaccine, which may serve as a feasible and effective therapeutic approach for lung cancer. Methods We predicted candidate neo-antigens according to the mutant gene analysis by sequencing the mouse Lewis cells and C57BL/6 mouse tail tissue. RNA vaccine was prepared with the neo-antigens as the template. We assessed antitumor efficacy, cytokine secretion and pathological changes after adoptive transfer of NRT cells in vitro and vivo experiments. Results We identified 10 non-synonymous somatic mutations and successfully generated NRT cells. The percentage of T-cell activation proportion was increased from 0.072% in conventional T cells to 9.96% in NRT cells. Interferon-γ secretion augmented from 17.8 to 24.2% as well. As an in vivo model, adoptive NRT cell infusion could promote active T-cell infiltration into the tumour tissue and could delay tumour progression. Conclusion NRT cells induced by RNA mutanome vaccine exert a significant anti-tumour effect in mouse lung cancer, and adoptive NRT cell therapy might be considered a feasible, effective therapeutic approach for lung cancer.

Details

ISSN :
14321335 and 01715216
Volume :
147
Database :
OpenAIRE
Journal :
Journal of Cancer Research and Clinical Oncology
Accession number :
edsair.doi.dedup.....13040567dbdc23a0d4eb950ad9374234