A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A24 carcinoma cells.
"Cancer-germline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in other normal tissues. They encode tumor specific antigens that are used in cancer immunotherapy trials. MAGE-4 antigens represent promising targets for cancer immunotherapy because gene MAGE-4 is expressed in more than 50% of carcinomas of the esophagus, lung, bladder, and head and neck. To identify new MAGE-4 antigenic peptides, we have folded HLA-A*2402 soluble molecules with candidate peptide NYKRCFPVI, which corresponds to amino acids 143 to151 of the MAGE-4 protein. A24/MAGE-4 multimers were used to isolate a cytolytic T cell clone that recognized the MAGE-4 peptide from the blood cells of a donor without cancer. This clone lysed specifically A24 carcinoma cells expressing MAGE-4. The antigenic peptide is processed more efficiently in tumor cells pre-treated with IFN-gamma. This MAGE-4 peptide could represent an interesting target for immunotherapy because it is presented by HLA-A24 molecules, which are widely expressed in different ethnic groups.
Ottaviani
Sabrina
S
Ludwig Institute for Cancer Research and Institute of Cellular Pathology, Cellular Genetics Unit, Université de Louvain, 74 avenue Hippocrate, UCL 7459, B-1200 Brussels, Belgium.
Colau
Didier
D
van der Bruggen
Pierre
P
van der Bruggen
Pierre
P
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019556:COS Cells; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D004854:Herpesvirus 4, Human; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma