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Solid cancers are highly refractory to conventional therapies and urgently need alternative treatments. We showed in previous work that tumour-directed dendritic cell vaccines (DC) when applied during oncolytic virus-mediated tumour inflammation (referred to as ODC) successfully triggers a CD8 T-cell response against model-antigens in mice.
The central aim of this study was to identify tumour-associated neoantigens suitable to investigate the efficacy of ODC treatment. Therefore, we performed transcriptomic sequencing and epitope prediction leading to detection of the neoepitope Ndufs1-V491A which is present in the NSCLC cell line CMT64 and the HCC cell line Hepa1.6. Elispot assays showed that intratumoural infection of subcutaneous (s.c.) CMT64-tumours on C57Bl/6 mice with oncolytic adenovirus induced significant T-cell responses against Ndufs1-V491A that were significantly less reactive to the wild type peptide. FACS analyses demonstrated neoepitope-specific T-cell responses after Ndufs1-V491A-directed DC vaccination that were additionally amplified by ODC. This ODC treatment was furthermore capable of inducing neoantigen-specific cytotoxicity as shown by in vivo CTL analyses. Finally, we established an Ndufs1-V491A-specific pentamer that allows functional investigations on Ndufs1-V491A-specific CD8 cells.
In summary, we established the neoantigen Ndufs1-V491A which is well suited to investigate tumour-directed CD8 T-cells raised by various immunotherapeutic approaches in murine tumour models.
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