MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model

Abstract A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptid...

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Bibliographic Details
Published in:Vaccine 2007-02, Vol.25 (9), p.1607-1618
Main Authors: Mukherjee, P, Pathangey, L.B, Bradley, J.B, Tinder, T.L, Basu, G.D, Akporiaye, E.T, Gendler, S.J
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Applied microbiology
Biological and medical sciences
Cancer Vaccines - administration & dosage
Cancer Vaccines - chemistry
Cancer Vaccines - immunology
CD4-Positive T-Lymphocytes - immunology
Cell Line, Tumor
Colon
Colon cancer
Colonic Neoplasms - immunology
Colonic Neoplasms - physiopathology
Colonic Neoplasms - prevention & control
Colonic Neoplasms - therapy
Colorectal cancer
CpG ODN
Disease Models, Animal
Fundamental and applied biological sciences. Psychology
GM-CSF
Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor - immunology
Immune system
Immunization
Immunotherapy - methods
Interferon-gamma - biosynthesis
Lymphocyte Activation
Medical research
Medical sciences
Mice
Microbiology
MUC1
Mucin-1 - administration & dosage
Mucin-1 - immunology
Mucin-1 - metabolism
Mucins
Oligodeoxyribonucleotides - administration & dosage
Oligodeoxyribonucleotides - immunology
Peptides
T-Lymphocytes, Cytotoxic - immunology
Tumors
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
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Summary:Abstract A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-γ-producing CD4+ helper and CD8+ cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2006.11.007