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.
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-gamma 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.
Wang
J
J
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
Murakami
T
T
Hakamata
Y
Y
Ajiki
T
T
Jinbu
Y
Y
Akasaka
Y
Y
Ohtsuki
M
M
Nakagawa
H
H
Kobayashi
E
E
D000818:Animals; D019470:Biolistics; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006224:Cricetinae; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009061:Mouth Mucosa / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D019496:Cancer Vaccines; D017931:DNA Primers; D018076:DNA, Complementary; D008164:Luminescent Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D008156:Luciferases