Regulation and pharmacokinetics of inducible recombinant TRAIL expression

Abstract

TRAIL is a potent antitumor agent, but its potential toxicity to normal human tissues limits its clinical applications in future. Therapy of human tumors might benefit from the use of vectors enabling tight control of TRAIL expression in vivo. To this aim, we constructed an adenoviral vector carrying the RU486-dependent gene switch system for the regulable expression of recombinant TRAIL. Only was apoptotic recombinant TRAIL expressed and cytotoxicity observed upon binding of RU 486 to the inducible promoter. Expression levels and kinetics of recombinant TRAIL expression could be achieved by modulating the concentration of the inducer. As a broad implication, our data provide an alternative approach to circumvent the potential toxicity of TRAIL in future human trials and this system may be utilized to treat human cancer using a long-term expression vector. ©2007 Landes Bioscience.