MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.
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-gamma-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.
Mukherjee
P
P
Mayo Clinic College of Medicine, Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, United States. mukherjee.pinku@mayo.edu
Pathangey
L B
LB
Bradley
J B
JB
Tinder
T L
TL
Basu
G D
GD
Akporiaye
E T
ET
Gendler
S J
SJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D018396:Mucin-1 / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D009077:Mucins; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines; D018396:Mucin-1; D009077:Mucins; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor