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. Ho wever, intravenous cytokine delivery is often inefficient and frequent ly accompanied by systemic toxicity. the goal of this study was to eva luate 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-galactosidas e, luciferase, interleukin-2, interleukin-6, and granulocyte-macrophag e colony stimulating factor (GM-CSF) complementary DNA (cDNA) into the oral mucosa and epidermis of healthy dogs resulted in effective, loca lized, transgenic protein expression. Additionally, the epidermal site s transfected with GM-CSF developed a profound inflammatory reaction c haracterized by neutrophilic infiltration. Clinical pathology analyses were unremarkable. These results demonstrate that in vivo particle-me diated gene transfer of canine oral mucosa and epidermis with cytokine cDNA can result in production of biologically active transgenic cytok ines with minimal toxicity. These findings have applications to cancer immunotherapy using a gene gun approach.