Abstract
alpha-Fetoprotein (AFP) is a potential target for immunotherapy in hepatocellular carcinoma; both the murine and human T-cell repertoires can recognize AFP-derived epitopes in the context of the MHC. Protective immunity can be generated with AFP-engineered dendritic cell-based vaccines. We now report a DNA-based immunization strategy using a prime-boost approach: coadministration of plasmid DNA encoding murine AFP and murine granulocyte-macrophage colony-stimulating factor followed by boosting with an AFP-expressing nonreplicating adenoviral vector. This immunization strategy can elicit a high frequency of Th1-type AFP-specific cells leading to tumor protective immunity in mice at levels comparable with AFP-engineered dendritic cells. This cell-free mode of immunization is better suited for large-scale vaccine efforts for patients with hepatocellular carcinoma.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Animals
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Cancer Vaccines / genetics*
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Cancer Vaccines / immunology*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / immunology
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Carcinoma, Hepatocellular / therapy*
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Epitopes, T-Lymphocyte / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology
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HLA-A2 Antigen / genetics
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HLA-A2 Antigen / immunology
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Humans
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Immunodominant Epitopes / genetics
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Immunodominant Epitopes / immunology*
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Immunotherapy, Active / methods
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Jurkat Cells / immunology
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Jurkat Cells / metabolism
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Liver Neoplasms / genetics
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Liver Neoplasms / immunology
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Liver Neoplasms / therapy*
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Plasmids / genetics
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T-Lymphocytes / immunology
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Transfection
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology
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alpha-Fetoproteins / biosynthesis
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alpha-Fetoproteins / genetics*
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alpha-Fetoproteins / immunology*
Substances
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Cancer Vaccines
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Epitopes, T-Lymphocyte
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HLA-A2 Antigen
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Immunodominant Epitopes
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Peptide Fragments
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Vaccines, DNA
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alpha-Fetoproteins
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Granulocyte-Macrophage Colony-Stimulating Factor