If a tumor expresses high or low levels of normal p53, or a very low level of mutant p53, conditions are favorable for Advexin. Tumors with high levels of mutant p53 do not respond well to p53-related therapy. The healthy and mutant p53 biomarkers are easily discerned with standard lab techniques, Roth said immunohistochemical staining detects protein levels, while gene chip analysis reveals gene sequence.
Creation of Introgen
Roth found little interest in gene therapy from established pharmaceutical companies, so in 1994 he co-founded Introgen working through M. D. Anderson's Office of Technology Management.
Introgen has since grown into a publicly traded company on NASDAQ, and while it still licenses important technology from M. D. Anderson, the company works broadly with other medical research institutions and biotech firms.
Introgen developed a commercial-grade version of the drug and advanced it through phase II and III clinical trials for head and neck cancer. Advexin(r) also is being tested in other cancers in a variety of clinical trials.
"If something's going to get to patients, it has to be commercialized," Roth said. The National Cancer Institute funds basic and translational research but simply cannot afford to fund large, late-stage clinical trials, he said.
Nanotechnology and p53
Roth and colleagues now focus on ways to deliver p53 and other tumor-suppressing genes systemically - through intravenous delivery. Advexin has to be injected straight into the tumor, but that's not workable for many cancers. Head and neck cancer kills patients by recurring, not spreading to other organs, but most cancer deaths involve metastasis.
By wrapping tumor-suppressing genes in tiny balls of fat, Roth and colleagues hope to be able to treat more invasive cancers. Whil
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center