Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas

Vaccine. 2007 Sep 28;25(39-40):6965-74. doi: 10.1016/j.vaccine.2007.06.063. Epub 2007 Jul 24.

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

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma / immunology
  • Adenoma / pathology
  • Adenoma / therapy*
  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / immunology
  • Disease Models, Animal*
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Immunotherapy
  • Intestinal Neoplasms / immunology
  • Intestinal Neoplasms / pathology
  • Intestinal Neoplasms / therapy*
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mucin-1* / administration & dosage
  • Mucin-1* / chemistry
  • Mucin-1* / genetics
  • Mucin-1* / immunology
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / immunology
  • Peptide Fragments* / administration & dosage
  • Peptide Fragments* / chemistry
  • Peptide Fragments* / genetics
  • Peptide Fragments* / immunology
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Cancer Vaccines
  • MUC1 tandem repeat peptide
  • Mucin-1
  • Oligodeoxyribonucleotides
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor