IN-VIVO CYTOKINE GENE-TRANSFER BY GENE GUN REDUCES TUMOR-GROWTH IN MICE

Implantation of tumor cells modified by in vitro cytokine gene transfe r has been shown by many investigators to result in potent in vivo ant itumor activities in mice. Here we describe an approach to tumor immun otherapy utilizing direct transfection of cytokine genes into tumor-be aring animals by particle-mediated gene transfer. In vivo transfection of the human interleukin 6 gene into the tumor site reduced methylcho lanthrene-induced fibrosarcoma growth, and a combination of murine tum or necrosis factor alpha and interferon gamma genes inhibited growth o f a renal carcinoma tumor model (Renca). In addition, treatment with m urine interleukin 2 and interferon gamma genes prolonged the survival of Renca tumor-bearing mice and resulted in tumor eradication in 25% o f the test animals. Transgene expression was demonstrated in treated t issues by ELISA and immunohistochemical analysis. Significant serum le vels of interleukin 6 and interferon gamma were detected, demonstratin g effective secretion of transgenic proteins from treated skin into th e bloodstream. This in vivo cytokine gene therapy approach provides a system for evaluating the antitumor properties of various cytokines in different tumor models and has potential utility for human cancer gen e therapy.