HAGE, a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides.
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.
Mathieu
Morgan G
MG
School of Biomedical and Natural Science, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK.
Knights
Ashley J
AJ
Pawelec
Graham
G
Riley
Catherine L
CL
Wernet
Dorothee
D
Lemonnier
François A
FA
Straten
Per Thor
PT
Mueller
Ludmila
L
Rees
Robert C
RC
McArdle
Stephanie E B
SE
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000378:metabolism*; D019496:Cancer Vaccines / Q000737:chemistry; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
C573563:ABCB5 protein, mouse; D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma; C412324:DDX43 protein, human; C573562:HAGE protein, mouse; D053487:DEAD-box RNA Helicases