Abstract
A bigenic MUC1.Tg/MIN mouse model was developed by crossing Apc/(MIN/+) (MIN) mice with human MUC1 transgenic mice to evaluate MUC1 antigen-specific immunotherapy of intestinal adenomas. The MUC1.Tg/MIN mice developed adenomas at a rate comparable to that of MIN mice and had similar levels of serum MUC1 antigen. A MUC1-based vaccine consisting of MHC class I-restricted MUC1 peptides, a MHC class II-restricted pan-helper peptide, unmethylated CpG oligodeoxynucleotide and GM-CSF caused flattening of adenomas and significantly reduced the number of large adenomas. Immunization was successful in generating a MUC1-directed immune response evidenced by increased MUC1 peptide-specific anti-tumor cytotoxicity and IFN-gamma secretion by lymphocytes.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenoma / immunology
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Adenoma / pathology
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Adenoma / therapy*
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Adjuvants, Immunologic
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Amino Acid Sequence
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Animals
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Cancer Vaccines* / administration & dosage
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Cancer Vaccines* / immunology
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Disease Models, Animal*
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology
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Humans
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Immunotherapy
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Intestinal Neoplasms / immunology
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Intestinal Neoplasms / pathology
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Intestinal Neoplasms / therapy*
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Male
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Mucin-1* / administration & dosage
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Mucin-1* / chemistry
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Mucin-1* / genetics
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Mucin-1* / immunology
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Oligodeoxyribonucleotides / administration & dosage
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Oligodeoxyribonucleotides / immunology
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Peptide Fragments* / administration & dosage
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Peptide Fragments* / chemistry
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Peptide Fragments* / genetics
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Peptide Fragments* / immunology
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Vaccination
Substances
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Adjuvants, Immunologic
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CPG-oligonucleotide
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Cancer Vaccines
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MUC1 tandem repeat peptide
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Mucin-1
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Oligodeoxyribonucleotides
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Peptide Fragments
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Granulocyte-Macrophage Colony-Stimulating Factor