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Gene gun–mediated oral mucosal transfer of interleukin 12 cDNA coupled with an irradiated melanoma vaccine in a hamster model: Successful treatment of oral melanoma and distant skin lesion

Cancer Gene Therapy volume 8, pages 705–712 (2001)Cite this article

Abstract

Malignant melanoma involving the oral cavity has a highly metastatic potential. Curative surgery is required to resect extensive oral tissues and often results in dysfunction as well as a severe cosmetic deformity in patients with the disease. An alternative technology for the local and sustained delivery of cytokines for cancer immunotherapy has been shown to induce tumor regression, suppression of metastasis, and development of systemic antitumor immunity. However, local immunization of the oral cavity has not previously been studied. In this study, we examined the efficacy of particle-mediated oral gene transfer on luciferase and green fluorescent protein production. The results showed that these proteins were more significantly expressed in oral mucosa than the skin, stomach, liver, and muscle. Using an established oral melanoma model in hamsters, particle-mediated oral gene gun therapy with interleukin (IL) 12 cDNA was then conducted. The results indicated that direct bombardment of mouse IL-12 cDNA suppressed tumor formation and improved the survival rate. The skin tumor model created by inoculation of melanoma cells was also significantly inhibited by the oral bombardment of IL-12 cDNA coupled with an irradiated melanoma vaccine administrated to the oral mucosa, compared to treatment with a percutaneous vaccine. IL-12 gene gun therapy, combined with an oral mucosal vaccine, induced interferon-γ mRNA expression in the host spleen for a long time. These results suggest that immunization of oral mucosa may induce systemic antitumor immunity more efficiently than immunization of the skin and that oral mucosa may be one of the most suitable tissues for cancer gene therapy by means of particle-mediated gene transfer. Cancer Gene Therapy (2001) 8, 705–712

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Acknowledgements

We thank T. Osumi (Himeji Institute of Technology, Hyogo, Japan) for donating a GFP plasmid, phGFP-105-C1, and S. Wolf (Genetic Institute, Cambridge, MA) for donating a murine IL-12 expression plasmid, pCAGGS-IL-12. We greatly appreciate the skillful technical assistance of Kyoko Okamaoto and Noriko Hayashi. This work was partially supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan. (No. 13470261)

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Authors and Affiliations

  1. Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi, 329-0498, Japan

    Jun Wang, Takashi Murakami, Yoji Hakamata, Takashi Ajiki & Eiji Kobayashi

  2. Department of Oral Surgery, Jichi Medical School, Tochigi, 329-0498, Japan

    Jun Wang, Yoshinori Jinbu & Yoko Akasaka

  3. Department of Dermatology, Jichi Medical School, Tochigi, 329-0498, Japan

    Takashi Murakami, Mamitaro Ohtsuki & Hidemi Nakagawa

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  1. Jun Wang
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Correspondence to Takashi Murakami.

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Wang, J., Murakami, T., Hakamata, Y. et al. Gene gun–mediated oral mucosal transfer of interleukin 12 cDNA coupled with an irradiated melanoma vaccine in a hamster model: Successful treatment of oral melanoma and distant skin lesion. Cancer Gene Ther 8, 705–712 (2001). https://doi.org/10.1038/sj.cgt.7700363

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