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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.
AuthorsT Kobayashi, C Lonchay, D Colau, N Demotte, T Boon, P van der Bruggen
JournalTissue antigens (Tissue Antigens) Vol. 62 Issue 5 Pg. 426-32 (Nov 2003) ISSN: 0001-2815 [Print] Denmark
PMID14617050 (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

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