RETROVIRAL DELIVERY AND TETRACYCLINE-DEPENDENT EXPRESSION OF IL-1-BETA-CONVERTING ENZYME (ICE) IN A RAT GLIOMA MODEL PROVIDES CONTROLLED INDUCTION OF APOPTOTIC DEATH IN TUMOR-CELLS

Interleukin 1 beta-converting enzyme (ICE) is a member of a growing fa mily of cysteine proteases shown to be a crucial component in the acti vation of a genetic program that leads to autonomous cell death in mam malian cells. In this study, a murine ICE-lacZ fusion gene was introdu ced into a novel retroviral vector designed to achieve regulated ectop ic expression of a foreign gene in mammalian-cells. By delivering the ICE-lacZ gene within a retroviral vector and under the control of a te tracycline-regulated promoter, we were able to utilize the intrinsic c ell death program of ICE as a means for tumoricidal therapy in a rat b rain tumor model. Both in culture and in vivo suppression of ICE-lacZ expression was extremely tight in the presence of tetracycline, as det ermined by the lack of X-galactosidase-positive tumor cells and by cel l viability. When tetracycline was withdrawn, ICE-lacZ gene expression was rapidly turned on and apoptosis-mediated cell death occurred in e ssentially all tumor cells.