TY - JOUR
T1 - HAGE, a cancer/testis antigen with potential for melanoma immunotherapy
T2 - identification of several MHC class I/II HAGE-derived immunogenic peptides
AU - Mathieu, Morgan G
AU - Knights, Ashley J
AU - Pawelec, Graham
AU - Riley, Catherine L
AU - Wernet, Dorothee
AU - Lemonnier, François A
AU - Straten, Per Thor
AU - Mueller, Ludmila
AU - Rees, Robert C
AU - McArdle, Stephanie E B
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - ATP Binding Cassette Transporter, Subfamily B
KW - ATP-Binding Cassette Transporters/biosynthesis
KW - Animals
KW - Antigen Presentation
KW - Antigens, Neoplasm/metabolism
KW - Cancer Vaccines/chemistry
KW - Cell Proliferation
KW - DEAD-box RNA Helicases/metabolism
KW - Dendritic Cells/cytology
KW - Epitopes/chemistry
KW - Humans
KW - Immunotherapy/methods
KW - Interferon-gamma/metabolism
KW - Major Histocompatibility Complex
KW - Melanoma/immunology
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Neoplasm Proteins/metabolism
KW - RNA, Messenger/metabolism
KW - T-Lymphocytes/metabolism
U2 - 10.1007/s00262-007-0331-2
DO - 10.1007/s00262-007-0331-2
M3 - Journal article
C2 - 17487488
SN - 0340-7004
VL - 56
SP - 1885
EP - 1895
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
IS - 12
ER -