ABSTRACT
Gene therapy involves the introduction of wild-type p53 via an adenoviral vector or oncolytic adenoviral expression. Gendicine and Advexin (INGN 201) are both examples of adenovirus based p53 therapy currently in clinical trials in the USA to treat head and neck cancer (Clayman et al. 1998, 1999; Han et al. 2003; Speetjens et al. 2009). Although, p53 adenoviral based therapies have shown some effi cacy in impeding tumor growth, some side effects have also been associated. Mild side effects, such as fever and injection site pain, have been observed in clinical trials (Pan et al. 2009). In addition, severe toxicity was observed, but this may be an effect of apoptotic signals from tumor cells on neighboring cells (Roth 2006). In contrast to gene therapy, where a wild-type copy of p53 is introduced in a non-discriminatory fashion and is incapable of self-replication, oncolytic virotherapy uses a different method to restore p53. In this strategy, the virus can replicate only in cancer cells (anti-viral response observed in normal cells) or replication of the virus is coupled to induction of oncogenes (Crompton and Kirn 2007; Bazan-Peregrino et al. 2008). Examples of such virotherapy are Onyx-015 (E1B deleted) (Bischoff et al. 1996; Heise et al. 1997), H101 (Xu et al. 2003; Yuan et al. 2003; Lu et al. 2004; Xia et al. 2004) and KH901 (Fujimoto et al. 2006; Mace et al. 2007; Shen et al. 2007; Chang et al. 2009). The oncolytic herpes simplex virus (HSV), ONCO-Vex GM-CSF, has also been tested in clinical trials; however, long term toxicity and recurrence data are not yet available (Fujimoto et al. 2006; Mace et al. 2007). This modality of treatment sounds promising, but the right dosage and route of administration for delivery of these non-replicating adenoviral vectors has to be inspected further.
