Novel vaccination protocol consisting of injecting MUC1 DNA and nonprimed dendritic cells at the same region greatly enhanced MUC1-specific antitumor immunity in a murine model.
In order to induce specific antitumor immunity in mice, we attempted to immunize C57BL/6 mice with DNA vaccine encoding MUC1 polypeptide. When the mice immunized with MUC1 DNA were challenged with EL4-muc, MUC1-transfected syngeneic lymphoma cells, they completely rejected tumors. When DNA vaccine was given to the EL4-muc tumor-bearing mice, this vaccination was insufficient to suppress tumor growth in the mice. However, activated, but nonprimed dendritic cells (DCs) obtained from syngeneic mice and MUC1 DNA vaccine were given simultaneously to the same site of EL4-muc tumor-bearing mice, tumor growth was markedly suppressed accompanying prolongation of survival time. MUC1 antigen was detected on the DCs at the vaccination site and in regional nodes in the mice which received MUC1 DNA vaccine and DCs. These mice showed markedly enhanced cellular immune responses specific for MUC1 compared to those in mice vaccinated with MUC1 DNA alone. No significant difference in titers of antibodies to MUC1 between the two groups was observed. These results suggest that nonprimed DCs inoculated at the DNA vaccine site are essential for eliciting strong antitumor cellular immunity to suppress tumor growth efficiently in DNA-vaccinated mice. This animal model is useful for developing DNA vaccine for anti-cancer immunotherapy.
Kontani
Keiichi
K
Second Department of Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan.
Taguchi
Osamu
O
Ozaki
Yoshitomo
Y
Hanaoka
Jun
J
Tezuka
Noriaki
N
Sawai
Satoru
S
Inoue
Shuhei
S
Fujino
Shozo
S
Maeda
Toshinaga
T
Itoh
Yasushi
Y
Ogasawara
Kazumasa
K
Sato
Hiroshi
H
Ohkubo
Iwao
I
Kudo
Toshio
T
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D008223:Lymphoma / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000235:genetics* / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage*
D015703:Antigens, CD; D018396:Mucin-1; D019444:Vaccines, DNA