Abstract
The unique immunoglobulin (Ig) idiotype on the surface of each B-cell lymphoma represents an ideal tumor-specific antigen for use as a therapeutic vaccine. We have used an Escherichia coli-based, cell-free protein-expression system to produce a vaccine within hours of cloning the Ig genes from a B-cell tumor. We demonstrated that a fusion protein consisting of an idiotypic single chain Fv antibody fragment (scFv) linked to a cytokine (GM-CSF) or to an immunostimulatory peptide was an effective lymphoma vaccine. These vaccines elicited humoral immune responses against the native Ig protein displayed on the surface of a tumor and protected mice against tumor challenge with efficacy equal to that of the conventional Ig produced in a mammalian cell and chemically coupled to keyhole limpet hemocyanin. The cell-free E coli system offers a platform for rapidly generating individualized vaccines, thereby allowing much more efficient application in the clinic.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / biosynthesis*
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / therapeutic use
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Antigens, Neoplasm / biosynthesis*
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Antigens, Neoplasm / radiation effects
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Cancer Vaccines / biosynthesis*
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology
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Cancer Vaccines / therapeutic use
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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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Humans
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Immunoglobulin Idiotypes / biosynthesis*
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Immunoglobulin Idiotypes / genetics
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Immunoglobulin Idiotypes / immunology
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Immunoglobulin Idiotypes / therapeutic use
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Immunoglobulin Variable Region / biosynthesis*
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Immunoglobulin Variable Region / genetics
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Immunoglobulin Variable Region / immunology
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Immunoglobulin Variable Region / therapeutic use
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Lymphoma, B-Cell / genetics
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Lymphoma, B-Cell / immunology
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Lymphoma, B-Cell / therapy*
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Mice
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / immunology
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Neoplasms, Experimental / therapy
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Recombinant Fusion Proteins / biosynthesis*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
Substances
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Antibodies, Monoclonal
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Antigens, Neoplasm
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Cancer Vaccines
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Immunoglobulin Idiotypes
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Immunoglobulin Variable Region
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Recombinant Fusion Proteins
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Granulocyte-Macrophage Colony-Stimulating Factor