Oncolytic viruses kill cells in part by modulating endogenous cell death pathways. The p53 tumor suppressor gene plays an important role in these cell death pathways. In cancer cells, p53-dependent pathways are usually disturbed.
The expression of p53 by oncolytic adenoviruses during their replication results in a rapid and effective killing of cancer cells and eradication of tumors in a wide variety of preclinical cancer models. Importantly, the increased toxicity of the virus against cancer cells did not compromise its safety relating to normal, non-malignant cells.
ORCA Therapeutics’ development pipeline contains several oncolytic adenoviruses expressing P53.
Publications:
Van Beusechem et al. Cancer Res.2002;
Geoerger et al. Cancer Res. 2004;
Geoerger et al. J. Gene Med. 2005;
Graat et al., Mol. Canc. Ther. 2007;
Heideman Mol Ther. 12. 2005;
Van Beusechem et al. Mol. Canc. Ther. 2005.