Chapter 21: Gene therapy and oncolytic virus therapy

Oncolytic viruses replicate selectively in tumor cells and have been explored as a targeted treatment approach against cancers [Bell (2007); Bell et al. (2003); Moon Crompton and Kirn (2007); Davis and Fang (2005); Kaplan (2005); Kelly and Russell (2007); Kirn and McCormick (1996); McCormick (2003, 2005); O'Shea (2005); Parato et al. (2005); Post et al. (2005); Roberts et al. (2006); Vähä-Koskela et al. (2007); Wong et al. (2010)]. In principle an oncolytic virus will spread though the tumor cell population and lyse the infected cells, leading to eradication or control of the tumor. Because of the selectivity of such viruses for cancer cells rather than normal human cells, side effects should also be less pronounced than those associated with traditional treatments, such as chemotherapy or ionizing radiation. Oncolytic virus therapy has been explored in the context of several different virus species. While some non-human viruses display natural selectivity for cancer cells in humans [Koppers-Lalic and Hoeben (2011)], modern approaches use genetically engineered viruses to achieve tumor selectivity. The first engineered virus generated in the 1990s was a herpes simplex virus-1 [Martuza et al. (1991)]. Engineered adenoviruses have been of major interest in recent clinical trials, especially in the context of head and neck cancer [Wong et al. (2010)]. Indeed the adenovirus H101 (Shanghai Sunway Biotech, Shanghai, China) was approved in China for the treatment of head and neck cancer in combination with chemotherapy [Garber (2006)]. A variety of other virus types has also been explored [Eager and Nemunaitis (2011)]. However despite initial promising results and observations in the laboratory and clinic, oncolytic viruses have so far failed to demonstrate sustained and reliable treatment success [Wong et al. (2010)]…