New MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A1 tumor cells.

Abstract

'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.

• Authors: T Kobayashi, C Lonchay, D Colau, N Demotte, T Boon, P van der Bruggen
• Journal: Tissue antigens (Tissue Antigens) Vol. 62 Issue 5 Pg. 426-32 (Nov 2003) ISSN: 0001-2815 [Print] England
• PMID: 14617050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• HLA-A1 Antigen
• MAGEA4 protein, human
• Neoplasm Proteins
• Peptides

Topics

• Antigens, Neoplasm
• Flow Cytometry
• HLA-A1 Antigen (immunology)
• Humans
• Neoplasm Proteins (immunology, metabolism)
• Peptides (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• Tumor Cells, Cultured