Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model
| Autor: | Amanda Maree Walmsley, M. Lucrecia Alvarez, Sandra J. Gendler, Hugh S. Mason, Julia Pinkhasov, Pinku Mukherjee, Teresa L. Tinder, Latha B. Pathangey |
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| Rok vydání: | 2010 |
| Předmět: |
Cholera Toxin
Cancer Research CpG Oligodeoxynucleotide medicine.medical_treatment Immunology Biology medicine.disease_cause Autoantigens digestive system Article Immune tolerance Mice Cell Line Tumor Immune Tolerance medicine Animals Humans Immunology and Allergy skin and connective tissue diseases neoplasms MUC1 Mucin-1 Mucin Cholera toxin Neoplasms Experimental Interleukin-12 Molecular biology biological factors digestive system diseases Mice Inbred C57BL Oligodeoxyribonucleotides Oncology Vibrio cholerae biology.protein Immunization Protein A Adjuvant Injections Intraperitoneal |
| Zdroj: | Cancer Immunology, Immunotherapy. 59:1801-1811 |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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