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

Citation
J. Wang 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, CANC GENE T, 8(10), 2001, pp. 705-712
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER GENE THERAPY
ISSN journal
0929-1903 → ACNP
Volume
8
Issue
10
Year of publication
2001
Pages
705 - 712
Database
ISI
SICI code
0929-1903(200110)8:10<705:GGOMTO>2.0.ZU;2-P
Abstract
Malignant melanoma involving the oral cavity has a highly metastatic potent ial. Curative surgery is required to resect extensive oral tissues and ofte n results in dysfunction as well as a severe cosmetic deformity in patients with the disease. An alternative technology for the local and sustained de livery of cytokines for cancer immunotherapy has been shown to induce tumor regression, suppression of metastasis, and development of systemic antitum or immunity. However, local immunization of the oral cavity has not previou sly been studied. In this study, we examined the efficacy of particle-media ted oral gene transfer on luciferase and green fluorescent protein producti on. The results showed that these proteins were more significantly expresse d in oral mucosa than the skin, stomach, liver, and muscle. Using an establ ished oral melanoma model in hamsters, particle-mediated oral gene gun ther apy 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 th e oral mucosa, compared to treatment with a percutaneous vaccine. IL-12 gen e gun therapy, combined with an oral mucosal vaccine, induced interferon-ga mma, mRNA expression in the host spleen for a long time. These results sugg est 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 parti cle-mediated gene transfer.