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 normal tissues. They encode shared tumor-specific Ags, which have been used in therapeutic vaccination trials of cancer patients. MAGE-3 is expressed in 74% of metastatic melanoma and in 50% of carcinomas of esophagus, head and neck, bladder, and lung. We report here the identification of a new MAGE-3 peptide, which is recognized by three different CD4(+) T cell clones isolated from a melanoma patient vaccinated with a MAGE-3 protein. These clones, which express different TCRs, recognize an HLA-DR1 peptide ACYEFLWGPRALVETS, which corresponds to the MAGE-3(267-282) and the MAGE-12(267-282) protein sequences. One of the T cell clones, which expresses LFA-1 at a high level, lysed tumor cells expressing DR1 and MAGE-3. Another of these DR1-restricted CD4(+) clones recognized not only the MAGE-3/12 peptide but also homologous peptides encoded by genes MAGE-1, 2, 4, 6, 10, and 11.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antigen Presentation* / genetics
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Antigens, Neoplasm / administration & dosage
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Antigens, Neoplasm / metabolism*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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Cancer Vaccines / administration & dosage*
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology*
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Cell Line, Transformed
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Cell Separation
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Cells, Cultured
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Clone Cells
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HLA-DR1 Antigen / metabolism*
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Humans
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Injections, Intradermal
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Melanoma / immunology*
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Melanoma / metabolism
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Melanoma / pathology
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Melanoma / prevention & control
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Melanoma-Specific Antigens
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Molecular Sequence Data
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Neoplasm Proteins / administration & dosage
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology
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Neoplasm Proteins / metabolism*
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Peptide Fragments / administration & dosage
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Fragments / metabolism*
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Proteins / metabolism
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Tumor Cells, Cultured
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / immunology
Substances
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Antigens, Neoplasm
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Cancer Vaccines
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HLA-DR1 Antigen
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MAGEA1 protein, human
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MAGEA10 protein, human
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MAGEA3 protein, human
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MAGEA4 protein, human
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MAGEL2 protein, human
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Mageb1 protein, mouse
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Mageb3 protein, mouse
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Magel2 protein, mouse
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Melanoma-Specific Antigens
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Neoplasm Proteins
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Peptide Fragments
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Proteins
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Vaccines, Synthetic