In vivo cytokine gene transfer by gene gun reduces tumor growth in mice.

Abstract

Implantation of tumor cells modified by in vitro cytokine gene transfer has been shown by many investigators to result in potent in vivo antitumor activities in mice. Here we describe an approach to tumor immunotherapy utilizing direct transfection of cytokine genes into tumorbearing animals by particle-mediated gene transfer. In vivo transfection of the human interleukin 6 gene into the tumor site reduced methylcholanthrene-induced fibrosarcoma growth, and a combination of murine tumor necrosis factor a and interferon y genes inhibited growth of a renal carcinoma tumor model (Renca). In addition, treatment with murine interleukin 2 and interferon -y genes prolonged the survival of Renca tumor-bearing mice and resulted in tumor eradication in 25% of the test animals. Transgene expression was demonstrated in treated tissues by ELISA and immunohistochemical analysis. Significant serum levels of interleukin 6 and interferon y were detected, demonstrating effective secretion of transgenic proteins from treated skin into the bloodstream. This in vivo cytokine gene therapy approach provides a system for evaluating the antitumor properties ofvarious cytokines in different tumor models and has potential utility for human cancer gene therapy.

In vitro and in vivo transfection of plasmid DNA in the Dunning prostate tumor R3327-AT1 is enhanced by focused ultrasound

“…[8][9][10][11][12][13][14]20 Also, the absolute number of the reported transfection efficiencies might vary since there was a 24 h interval between incubation with DNA/sonication and analysis. If cell proliferation takes place, transfected and nontransfected cells might divide not neccessarily at the same rate.…”

“…Accordingly, intratumoral cytokine gene transfer by gene guns has been reported to reduce tumor growth in vivo. 13 Moreover, a substantial level of gene expression was reported following less localized, i.v. delivery of plasmid vectors in vivo.…”

Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by cDNA-transfected tumor cells induces a more potent antitumor response than exogenous GM-CSF

“…8,9,20,23,26,29,36 When different cytokine genes were compared, GM-CSF most effectively prevented subsequent tumor growth in a poorly immunogenic tumor model. 20 We confirmed these findings in a similar protection model.…”

Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model

“…3,4 Additionally, therapeutic genes inserted into the vector may be infected into specific host tissues to produce a biological effect. 5,6 However, most viral vectors do not preferentially infect tumor cells. To prevent viral replication and subsequent toxicity to normal tissues, the E1A gene, which is critical for adenoviral replication, is frequently deleted.…”