Introgen Therapeutics, Inc., a leading developer of biopharmaceutical products, announced a Clinical Trials Agreement (CTA) with the Division of Cancer Treatment and Diagnosis (DCTD) of the National Cancer Institute (NCI) to co-develop Introgen's p53 based cancer agent Advexin. The initial study under this Agreement will be a phase 1/2 study. Advexin will be administered in the form of an oral rinse, or mouthwash for oral premalignancies. Positive data from more than 20 clinical studies support the utility of Advexin in the treatment of established malignant tumors, and this trial will be the first to investigate the effect of Advexin on oral lesions that are at high risk for developing into full blown cancers. The clinical trial, conducted by multiple investigators, will be sponsored by DCTD-NCI. Introgen has supplied Advexin to NCI for distribution to clinical investigators.

"Introgen has developed considerable skill in the clinical use of the p53 gene to treat established cancers," said Dr. James Merritt, Introgen's chief medical officer. "Cancer prevention is the ultimate goal, and the identification of critical genetic alterations in cancer, such as p53, represents in our view the most promising path to successful early disease intervention and prevention."

The goal of the study is to harness the body's own cancer control mechanisms in order to destroy those cells that may become malignant. To achieve this, patients with premalignant lesions will be treated for up to six months with Advexin delivered as an oral rinse. Once inside precancerous cells, Advexin leads to the expression of high levels of p53, a protein that plays a central role in the normal pathways that cause damaged cells to undergo apoptosis (also known as cell suicide).

Through a previous Cooperative Research and Development Agreement established in 1999, Introgen and the NCI initiated evaluation of Advexin as an anti-cancer agent for a variety of cancers including breast, ovarian, bladder, liver, lung and brain cancers. The CTA expands and extends development of Advexin for the treatment and prevention of cancer.

Tobacco smoking and alcohol use are contributing factors to the development of oral cancer and the American Cancer Society estimates that in 2003 more than 180,000 cancer deaths are expected to be caused by tobacco use. It is estimated that 30,000 new cases of oral cavity cancer occur annually. Cancers of the oropharynx occur in approximately 4,000 patients annually in the United States. Frequently, cancers in this region of the body recur after surgery, chemotherapy, and radiotherapy; consequently new approaches to preventing recurrence are needed.

Advexin supplies p53 protein in very high concentrations in cancer tissue which selectively kills cancer cells while not harming the surrounding normal cells. P53 is a normal constituent of cells and is known as a tumor suppressor because it provides a powerful halt signal on cell growth. One of the major roles of this protein is to recognize when the cell has been damaged by mutation and to stop cell growth until the damage is repaired. If the cell is heavily damaged and beyond repair, p53 initiates the cell death pathway to prevent the cell from growing out of control. Scientists refer to this process as apoptosis. Apoptosis, or cell death, is a normal process that the body uses to eliminate damaged cells, precancerous cells and cells that are no longer necessary.