Vaccination of mice with MUC1 cDNA suppresses the development of lung metastases.
C57BL/6 mice were immunized intradermally with various doses of purified pCEP4 plasmid DNA containing full-length MUC1 cDNA (22 tandem repeats). Mice immunized with MUC1 DNA three times at weekly intervals had serum antibodies to a synthetic peptide corresponding to the tandem repeats of MUC1. The antibody titer correlated with the plasmid DNA dose. After the third immunization mice were injected intravenously with 5 x 10(5) 16-F10 melanoma cells that had been stably transfected with MUC1 cDNA (F10-MUC1-C8 clone cells). The number of lung metastatic nodules three weeks after inoculation of F10-MUC1-C8 cells was significantly lower in mice immunized with MUC1 plasmid DNA than in mice immunized with the vector DNA alone. Thus, the suppression of lung metastasis was antigen-specific. In vivo depletion of lymphocyte subpopulations by specific antibodies revealed that natural killer cells are the major effector cells responsible for the suppression of lung metastasis. CD4+ cells and CD8+ cells apparently played some roles too.
Kamata
Mika
M
Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo,Japan.
Denda-Nagai
Kaori
K
Kubota
Nobuyoshi
N
Aida
Satoshi
S
Takeda
Kazuyoshi
K
Irimura
Tatsuro
T
D000818:Animals; D019496:Cancer Vaccines; D018076:DNA, Complementary / Q000008:administration & dosage*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000008:administration & dosage / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms
D019496:Cancer Vaccines; D018076:DNA, Complementary; D018396:Mucin-1