In vivo particle-mediated cytokine gene transfer into canine oral mucosa and epidermis.
Cytokines can stimulate immune effector cells present within the oral mucosa and epidermis to respond to vaccination or to combat cancer. However, intravenous cytokine delivery is often inefficient and frequently accompanied by systemic toxicity. The goal of this study was to evaluate dogs as a large animal model for gene therapy of cancer because they develop spontaneous oral and epidermal tumors. In this report, we demonstrate that particle-mediated gene transfer of beta-galactosidase, luciferase, interleukin-2, interleukin-6, and granulocyte-macrophage colony stimulating factor (GM-CSF) complementary DNA (cDNA) into the oral mucosa and epidermis of healthy dogs resulted in effective, localized, transgenic protein expression. Additionally, the epidermal sites transfected with GM-CSF developed a profound inflammatory reaction characterized by neutrophilic infiltration. Clinical pathology analyses were unremarkable. These results demonstrate that in vivo particle-mediated gene transfer of canine oral mucosa and epidermis with cytokine cDNA can result in production of biologically active transgenic cytokines with minimal toxicity. These findings have applications to cancer immunotherapy using a gene gun approach.
Keller
E T
ET
Institute on Aging, University of Wisconsin, Madison 53706, USA.
Burkholder
J K
JK
Shi
F
F
Pugh
T D
TD
McCabe
D
D
Malter
J S
JS
MacEwen
E G
EG
Yang
N S
NS
Ershler
W B
WB
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D004285:Dogs; D004817:Epidermis / Q000502:physiology*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D009061:Mouth Mucosa / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000096:biosynthesis
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008156:Luciferases; D001616:beta-Galactosidase