Efficient adenoviral transfer of NF-kappa B inhibitor sensitizes melanoma to tumor necrosis factor-mediated apoptosis

It has been suggested that the in vitro cytotoxicity of tumor necrosis fact or (TNF) toward a number of transformed cell lines could make it a useful a gent for anti-tumor therapy. However, many tumor cell lines are resistant t o TNF-induced cell death. It has been shown that transcription factors of t he NF-kappa B family, which are themselves activated by TNF, could protect cells against apoptotic cell death. To test whether melanoma cells, which a re normally resistant to TNF-mediated killing, can be made susceptible by i nhibiting the activation of NF-kappa B, we generated a recombinant adenovir us expressing a dominant mutant form of I kappa B alpha under the control o f a CMV promoter. We show here that adenovirus-mediated inhibition of NF-ka ppa B function rendered melanoma cells susceptible to the cytotoxic effects of TNF, and thus that NF-kappa B-inhibiting adenoviruses could become usef ul adjuvants in TNF-based anti-tumor therapies. (C) 1999 Wiley-Liss, Inc.