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

• Published in: Vaccine Vol. 25; no. 39; pp. 6965 - 6974
• Main Authors: Akporiaye, Emmanuel T, Bradley-Dunlop, Deborah, Gendler, Sandra J, Mukherjee, Pinku, Madsen, Cathy S, Hahn, Tobias, Besselsen, David G, Dial, Sharon M, Cui, Haiyan, Trevor, Katrina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 28-09-2007; Elsevier Limited
• Subjects: Adenoma; Adenoma - immunology; Adenoma - pathology; Adenoma - therapy; Adjuvants, Immunologic; Allergy and Immunology; Amino Acid Sequence; Animals; Antigens; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Colleges & universities; Colorectal cancer; Cytotoxicity; Disease Models, Animal; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Humans; Immune response; Immunization; Immunotherapy; Intestinal Neoplasms - immunology; Intestinal Neoplasms - pathology; Intestinal Neoplasms - therapy; Laboratories; Lymphocytes; Male; Mice; Mice, Transgenic; Molecular Sequence Data; MUC1.Tg/MIN mice; 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; Peptides; Proteins; Rodents; Tumors; Vaccination; PBS; granulocyte-macrophage colony stimulating factor; COX-2; IFA; unmethylated cytosine-guanine oligodeoxynucleotide; cyclooxygenase-2; multiple intestinal neoplasia; phosphate-buffered saline; Adenoma; MUC1.Tg/MIN mice; MUC1 transgenic; MUC1; incomplete Freund's adjuvant; MIN; GM-CSF; mucin; Immunotherapy; CpG-ODN; MUC1.Tg
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.06.063

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-γ secretion by lymphocytes.