New MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A1 tumor 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 shared tumor-specific antigens, which have been used in small therapeutic vaccination trials of cancer patients. Gene MAGE-4, which is expressed in more than 50% of carcinomas of esophagus, head and neck, lung, and bladder, has two known alleles. Using PCR amplifications and digestions of the amplified product, we found that one third of the MAGE-4-positive samples expressed MAGE-4a. We folded HLA-A1 tetramers with peptide MAGE-4a169-177 EVDPASNTY, which is homologous to MAGE-1- and MAGE-3-encoded peptides recognized on HLA-A1 by cytolytic T lymphocytes. Blood lymphocytes from an individual without cancer were directly labelled with these A1/MAGE-4 tetramers. The very rare cells that were stained were sorted by flow cytometry and cloned. We isolated a cytolytic T-lymphocyte clone that lyzed specifically cells pulsed with this MAGE-4 peptide and HLA-A1 tumor cells expressing MAGE-4a, demonstrating that this antigenic peptide is processed efficiently in tumor cells. This peptide might therefore be useful for therapeutic antitumoral vaccination.
Kobayashi
T
T
Kirin Brewery Co., Cellular Immunotherapy, Japan.
Lonchay
C
C
Colau
D
D
Demotte
N
N
Boon
T
T
van der Bruggen
P
P
D000951:Antigens, Neoplasm; D005434:Flow Cytometry; D015788:HLA-A1 Antigen / Q000276:immunology; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015788:HLA-A1 Antigen; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D010455:Peptides