Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model

Julia Pinkhasov, M. Lucrecia Alvarez, Latha B. Pathangey, Teresa L. Tinder, Hugh Mason, Amanda M. Walmsley, Sandra J. Gendler, Pinku Mukherjee

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.

Original languageEnglish (US)
Pages (from-to)1801-1811
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume59
Issue number12
DOIs
StatePublished - Dec 1 2010

Keywords

  • Cholera toxin B subunit
  • Epithelial mucin 1
  • MUC1 transgenic mouse model
  • Oral immunization
  • Tumor immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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    Pinkhasov, J., Alvarez, M. L., Pathangey, L. B., Tinder, T. L., Mason, H., Walmsley, A. M., Gendler, S. J., & Mukherjee, P. (2010). Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model. Cancer Immunology, Immunotherapy, 59(12), 1801-1811. https://doi.org/10.1007/s00262-010-0906-1