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

• Published in: Journal of cancer research and clinical oncology 2021-11, Vol.147 (11), p.3255-3268
• Main Authors: Sun, Jiaxing, Zhang, Jing, Hu, Haiyan, Qin, Huan, Liao, Ximing, Wang, Feilong, Zhang, Wei, Yin, Qi, Su, Xiaoping, He, Yanan, Li, Wenfeng, Wang, Kun, Li, Qiang
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Animals; Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antitumor activity; Cancer Research; Cancer vaccines; Cancer Vaccines - immunology; Cancer Vaccines - pharmacology; Carcinoma, Lewis Lung - genetics; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - therapy; Cell activation; Cell Line, Tumor; Cell therapy; Female; Hematology; Immunotherapy; Immunotherapy, Adoptive - methods; Interferon-gamma - immunology; Internal Medicine; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - therapy; Lymphocytes T; Male; Medicine; Medicine & Public Health; Metastases; Mice; Mice, Inbred C57BL; mRNA Vaccines; Mutation; Oncology; Original Article – Cancer Research; Original – Cancer Research; Point Mutation; Random Allocation; Ribonucleic acid; RNA; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Tumor Necrosis Factor-alpha - immunology; Tumors; Vaccines; Vaccines, Synthetic - immunology; Vaccines, Synthetic - pharmacology; γ-Interferon
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03735-y

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.