An additional ORF on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-speciWc T cells in the HLA-A2 context

International audienceWe characterized a new melanoma antigen derived from one of the multiple open reading frames (ORFs) of the meloe transcript. The meloe gene is overex-pressed in melanomas as compared to other cancer cell lines and normal tissues. The corresponding transcript is rather unusual, in that it does not contain a long unique ORF but multiple short ORFs. We recently characterized a tumor epitope derived from a polypeptide (MELOE-1) encoded by the ORF 1230-1370 and involved in relapse prevention of melanoma patients treated with autologous tumor inWltrating lymphocytes (TIL). Here we show that the ORF 285-404 encodes a polypeptide called MELOE-2 that also generated a HLA-A2 epitope recognized by a mela-noma-speciWc T cell clone derived from the same TIL population from which we derived the MELOE-1-speciWc T cell clone. We also showed that HLA-A2 melanoma cells were spontaneously recognized by the MELOE-2-speciWc T cell clone, and we detected the presence of MELOE-2 reactive T cells in another TIL population infused to a patient who remained relapse-free after TIL treatment. These results demonstrate that translation of meloe transcript in melanoma cells can produce at least two immuno-genic polypeptides, MELOE-1 and MELOE-2, from two distinct ORFs that could be relevant target for melanoma immunotherapy