Oncolytic (replication-competent) adenoviruses as anticancer agents.

IMPORTANCE OF THE FIELD: Whilst therapies for neoplasies have advanced tremendously in the last few decades, there is still a need for new anti-cancer treatments. One option is genetically-engineered oncolytic adenovirus (Ad) 'vectors'. These kill cancer cells via the viral replication cycle, and amplify the anti-tumor effect by producing progeny virions able to infect neighboring tumor cells. AREAS COVERED IN THIS REVIEW: We provide a description of basic Ad biology and summarize the literature for oncolytic Ads from 1996 to the present. WHAT THE READER WILL GAIN: An overall view of oncolytic Ads, the merits and drawbacks of the various features of these vectors, and obstacles to further development and future directions for research. TAKE HOME MESSAGE: Ads are attractive for gene therapy because they are relatively innocuous, easy to produce in large quantities, genetically stable, and easy to manipulate. A variety of have been constructed and tested, in pre-clinical and clinical experiments. Oncolytic Ads proved to be remarkably safe; no dose-limiting toxicity was observed in any clinical trial, and the maximum tolerated dose was not reached. At present, the major challenge for researchers is to increase the efficacy of the vectors, and to incorporate oncolytic virotherapy into existing treatment protocols.