Abstract
We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with detectable disease, following vaccination with a recombinant ALVAC virus, which bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented by HLA-A1. To evaluate the anti-MAGE CTL responses, we resorted to antigenic stimulation of blood lymphocytes under limiting dilution conditions, followed by tetramer analysis and cloning of the tetramer-positive cells. The clones were tested for their specific lytic ability and their TCR sequences were obtained. Four patients who showed tumor regression were analyzed, and an anti-MAGE-3.A1 CTL response was observed in three of these patients. Postvaccination frequencies of anti-MAGE-3.A1 CTL were 3 x 10(-6), 3 x 10(-3), and 3 x 10(-7) of the blood CD8 T cells, respectively. These three responses were monoclonal. No anti-MAGE-1.A1 CTL response was observed. These results indicate that, like peptide immunization, ALVAC immunization produces monoclonal responses. They also suggest that low-level antivaccine CTL responses can initiate a tumor regression process. Taken together, our analysis of anti-MAGE-3.A1 T cell responses following peptide or ALVAC vaccination shows a degree of correlation between CTL response and tumor regression, but firm conclusions will require larger numbers.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Canarypox virus / genetics
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Canarypox virus / immunology*
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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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Clone Cells
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Female
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Humans
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Injections, Intradermal
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Injections, Subcutaneous
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Lymphatic Metastasis / immunology
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Lymphatic Metastasis / prevention & control
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Melanoma / immunology*
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Melanoma / prevention & control*
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Melanoma / secondary
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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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Polymerase Chain Reaction
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Receptors, Antigen, T-Cell / biosynthesis
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Receptors, Antigen, T-Cell / blood
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Vaccines, Subunit / administration & dosage
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Vaccines, Subunit / genetics
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Vaccines, Subunit / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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Viral Vaccines / administration & dosage
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Viral Vaccines / genetics
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Viral Vaccines / immunology
Substances
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ALVAC vaccine
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Antigens, Neoplasm
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Cancer Vaccines
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MAGEA3 protein, human
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Neoplasm Proteins
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Receptors, Antigen, T-Cell
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Vaccines, Subunit
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Vaccines, Synthetic
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Viral Vaccines