HAGE, a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides

• Published in: Cancer Immunology, Immunotherapy Vol. 56; no. 12; pp. 1885 - 1895
• Main Authors: Mathieu, Morgan G, Knights, Ashley J, Pawelec, Graham, Riley, Catherine L, Wernet, Dorothee, Lemonnier, François A, Straten, Per Thor, Mueller, Ludmila, Rees, Robert C, McArdle, Stephanie E B
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.12.2007; Springer Verlag; Springer-Verlag
• Subjects: Animals; Antigen Presentation; Antigens; Antigens, Neoplasm - metabolism; ATP Binding Cassette Transporter, Subfamily B; ATP-Binding Cassette Transporters - biosynthesis; Cancer; Cancer Vaccines - chemistry; Cell Proliferation; DEAD-box RNA Helicases - metabolism; Dendritic Cells - cytology; Epitopes - chemistry; Genes; Humans; Immunology; Immunotherapy; Immunotherapy - methods; Interferon-gamma - metabolism; Life Sciences; Lymphocytes; Major Histocompatibility Complex; Melanoma; Melanoma - immunology; Melanoma - therapy; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Proteins - metabolism; Original; Peptides; Proteins; RNA, Messenger - metabolism; T-Lymphocytes - metabolism; Transgenic animals; Tumors; Germany
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-007-0331-2

There remains a need to identify novel epitopes of potential tumour target antigens for use in immunotherapy of cancer. Here, several melanoma tissues and cell lines but not normal tissues were found to overexpress the cancer-testis antigen HAGE at the mRNA and protein level. We identified a HAGE-derived 15-mer peptide containing a shorter predicted MHC class I-binding sequence within a class II-binding sequence. However, only the longer peptide was found to be both endogenously processed and immunogenic for T cells in transgenic mice in vivo, as well as for human T cells in vitro. A different class I-binding peptide, not contained within a longer class II sequence, was subsequently found to be both immunogenic and endogenously processed in transgenic mice, as was a second class II epitope. These novel HAGE-derived epitopes may contribute to the range of immunotherapeutic targets for use in cancer vaccination programs.