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| Original Article |
| 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 |
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| Keiichi Kontani1, Osamu Taguchi2, Yoshitomo Ozaki1, Jun Hanaoka1, Noriaki Tezuka1, Satoru Sawai1, Shuhei Inoue1, Shozo Fujino1, Toshinaga Maeda3, Yasushi Itoh4, Kazumasa Ogasawara4, Hiroshi Sato5, Iwao Ohkubo3 and Toshio Kudo6 |
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1Second Department of Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan
2Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
3Department of Medical Biochemistry, Shiga University of Medical Science, Otsu 520-2192, Japan
4Department of Pathology, Shiga University of Medical Science, Otsu 520-2192, Japan
5Department of Biology, Shiga University of Medical Science, Otsu 520-2192, Japan
6Cell Resource Center for Biochemical Research, Institute of Department, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
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Correspondence to: Dr Keiichi Kontani, Second Department of Surgery, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan. E-mail: konbat@belle.shiga-med.ac.jp |
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| Abstract |
| 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. Cancer Gene Therapy (2002) 9, 330-337 DOI: 10.1038/sj/cgt/7700444 |
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| Keywords |
| DNA vaccine; MUC1; cancer immunotherapy; dendritic cell |
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| Received 17 December 2001 |
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| April 2002, Volume 9, Number 4, Pages 330-337 |
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