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

P. Mukherjee; L. B. Pathangey; J. B. Bradley; T. L. Tinder; G. D. Basu; E. T. Akporiaye; S. J. Gendler

doi:10.1016/j.vaccine.2006.11.007

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

P. Mukherjee, L. B. Pathangey, J. B. Bradley, T. L. Tinder, G. D. Basu, E. T. Akporiaye, S. J. Gendler

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1607-1618
Number of pages	12
Journal	Vaccine
Volume	25
Issue number	9
DOIs	https://doi.org/10.1016/j.vaccine.2006.11.007
State	Published - Feb 19 2007

Keywords

Colon cancer
CpG ODN
GM-CSF
MUC1

ASJC Scopus subject areas

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2006.11.007

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title = "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-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.",

keywords = "Colon cancer, CpG ODN, GM-CSF, MUC1",

author = "P. Mukherjee and Pathangey, {L. B.} and Bradley, {J. B.} and Tinder, {T. L.} and Basu, {G. D.} and Akporiaye, {E. T.} and Gendler, {S. J.}",

note = "Funding Information: This work was supported by the SPORE in Gastrointestinal Cancers NIH P50 CA95060 and by the Mayo Foundation. We would like to thank Drs. D. Kufe and J. Schlom for providing the MC38.MUC1 and MC38.neo cell lines. We also thank Marvin Ruona in the Visual Communications core for preparing the figures in the correct format, Irene Beauvais for her assistance in submitting the manuscript, Dr. Joe Hentz and Noble Brie in the Biostatistics core for performing the statistical analysis and all technicians in the animal core facility for help in maintaining our mice.",

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AU - Pathangey, L. B.

AU - Bradley, J. B.

AU - Tinder, T. L.

AU - Basu, G. D.

AU - Akporiaye, E. T.

AU - Gendler, S. J.

N1 - Funding Information: This work was supported by the SPORE in Gastrointestinal Cancers NIH P50 CA95060 and by the Mayo Foundation. We would like to thank Drs. D. Kufe and J. Schlom for providing the MC38.MUC1 and MC38.neo cell lines. We also thank Marvin Ruona in the Visual Communications core for preparing the figures in the correct format, Irene Beauvais for her assistance in submitting the manuscript, Dr. Joe Hentz and Noble Brie in the Biostatistics core for performing the statistical analysis and all technicians in the animal core facility for help in maintaining our mice.

PY - 2007/2/19

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N2 - 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.

AB - 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.

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

Abstract

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