Identification of expressed endogenous retroviral element associated long terminal repeats in devil facial tumour cells

Abstract

Abstract The Tasmanian devil (Sarcophilus harrisii) population has undergone a major decline in the wild owing to the epidemics of two transmissible cancers known as devil facial tumours (DFT1 and DFT2). A multipronged conservation strategy is in place, but a vaccine that prevents devils from developing devil facial tumour disease would be a major step towards recovering the wild devil population. Critical to an effective DFT vaccine are target antigens. Putative non-coding regions of genomes have been identified as potential tumour-specific antigens for human cancer. These non-coding regions include long terminal repeats (LTRs) of endogenous retroviral elements (ERVs). We identified 11 193 ERV LTR transcripts that were expressed in DFT1 or DFT2 transcriptomes but not in healthy tissue samples. Using a proteogenomic approach, we identified 33 ERV LTR peptides unique to DFT1 and/or DFT2 immunopeptidomes; five of these were validated in subsequent screens with synthetic peptides. The ERV LTR peptides identified in this study can be tested as vaccine targets in DFT1 and DFT2 vaccines. This method can be applied to other species for the development of cancer vaccine targets that may be shared across tumour types.