title: An additional ORF on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context.
abstract: We characterized a new melanoma antigen derived from one of the multiple open reading frames (ORFs) of the meloe transcript. The meloe gene is overexpressed 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 infiltrating 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 melanoma-specific T cell clone derived from the same TIL population from which we derived the MELOE-1-specific T cell clone. We also showed that HLA-A2 melanoma cells were spontaneously recognized by the MELOE-2-specific 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 immunogenic polypeptides, MELOE-1 and MELOE-2, from two distinct ORFs that could be relevant target for melanoma immunotherapy.
authors.affiliation: CRCNA, Institut de Recherche Therapeutique, Université de Nantes, UMR INSERM U, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Godet
authors.forename: Agnès
authors.initials: A
authors.lastname: Moreau-Aubry
authors.forename: Dimitri
authors.initials: D
authors.lastname: Mompelat
authors.forename: Virginie
authors.initials: V
authors.lastname: Vignard
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
authors.forename: Francois
authors.initials: F
authors.lastname: Lang
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labarriere
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D001483:Base Sequence; D002986:Clinical Trials as Topic; D018076:DNA, Complementary / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D016366:Open Reading Frames / Q000276:immunology*; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D015789:HLA-A2 Antigen; C423726:MART-2 protein, human; C547554:MELOE-2 antigen, human; D009363:Neoplasm Proteins