Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Virus-directed enzyme prodrug therapy utilizing the bacterial enzyme nitroreductase delivered by a replication-defective adenovirus vector to activate the prodrug CB1954 is a promising strategy currently undergoing clinical trials in patients with a range of cancers. Similarly, selectively replicating oncolytic adenoviruses are entering clinical trials. An understanding of interactions between vector and target cell are critical to the development of these strategies. We demonstrate that adenovirus vectors activate cellular pathways that promote cell survival in an NF-kappaB-dependent manner, and consequently have a negative effect on the efficacy of cell killing induced by cancer gene therapy strategies. This provides a potential therapeutic target to enhance the cytotoxicity of these approaches.

Original publication

DOI

10.1038/sj.gt.3302510

Type

Journal article

Journal

Gene Ther

Publication Date

08/2005

Volume

12

Pages

1187 - 1197

Keywords

Adenoviridae, Aziridines, Cell Line, Tumor, Enzyme Activation, Genetic Therapy, Genetic Vectors, Humans, NF-kappa B, Neoplasms, Nitroreductases, Oncolytic Virotherapy, Oncolytic Viruses, Prodrugs, Signal Transduction, Virus Replication