Chapel Hill - The University of North Carolina at Chapel Hill School of Medicine is one of nine medical centers nationally trying to determine if injections of a genetically modified common cold virus may be an effective treatment for recurrent head and neck cancer.
Under investigation is a form of adenovirus that's modified to selectively infect and destroy tumor cells only.
Unmodified, adenoviruses can infect and multiply in both cancer and normal cells, thereby killing all cells. One of the genes that enable the virus to replicate is E1B. This gene's protein inactivates the tumor suppressor gene, p53, which normally protects the cell from adenovirus infection. "Unless p53 is inactivated, adenoviruses cannot replicate," explained Wendell G. Yarbrough, MD, assistant professor of otolaryngology/head and neck surgery at UNC-CH. "About 50% of malignant head and neck tumors are made of cells with an inactivated p53 gene. Cancer cells are the only cells in the body in which p53 has been inactivated allowing for specific killing of cancer cells by the modified virus." Adenovirus with a mutated or deleted E1B gene will not produce the protein needed to inactivate p53. This means the virus replicates only in tumor cells, not in normal ones.
"And when this virus gets in a cancer cell with inactivated p53, it replicates, makes new adenoviruses, and then as part of its normal life cycle, it lyses or kills that cell and releases viruses that can then infect adjacent cancer cells," Yarbrough said.
Yarbrough, the principal investigator for UNC in this clinical trial, said therapy using E1B-mutated adenovirus ties in with his basic research on the gene ARF, an activator of p53. "In fact, we're now combining ARF with this virus to look at the effect of this combination on tumor cells."
The researcher notes that previous studies using adenoviruses as cancer therapy have relied on viruses unable to replicate. But the modified adenovirus developed by Ony
Contact: Leslie H. Lang
University of North Carolina School of Medicine