Gene therapy drug shows potential in cancer trials

Special to The Times

Among the most promising gene therapy trials are ones to treat various forms of cancer. More than 100 of these are in the works, taking a variety of approaches: using genes to ramp up the immune system or block the action of other, cancer-causing genes, to name a couple.

Most of these -- and, indeed, all gene therapy treatments -- are still in the early stages of development. But one therapy could be on the market in the U.S. within the year.

Named Advexin, the injectable medication contains a genetically engineered form of a gene, p53, inserted into a harmless virus.

In the Advexin therapy, the virus enters cells, where it produces a p53 protein.


The p53 gene is normally present in humans and controls the activity of more than 100 other genes. When it is functioning normally, it blocks the formation of tumors and may even make cancerous cells more vulnerable to chemotherapy and radiation.

But mistakes in the gene can develop in people’s tissues over time, and in rare cases people are born with such defects. Under both circumstances, the gene plays a key role in the development of cancers.

In fact, researchers estimate that p53 mutations are involved in at least half of all cancers, including ones of the lung, colon, breast, ovary, brain and lymph nodes.

Advexin is delivered in a number of ways: It can be directly injected into tumors or the bloodstream, or delivered orally in a mouthwash.


Results of small tests with several cancers including advanced ones of the breast and lung have been encouraging. In a 2004 study at the MD Anderson Cancer Center in Houston, for example, 12 patients with advanced breast cancer received several injections of Advexin, followed by a course of chemotherapy. Their tumors shrunk by nearly 80%, from about 8 centimeters in diameter to less than 2 centimeters.

A Japanese study reported this year involved 10 patients suffering from late-stage cancer of the esophagus who were no longer responding to conventional therapies. After receiving four Advexin injections, at one year 60% were still living. (Only a 20% survival rate would normally be expected.) In three patients, doctors found no evidence of the tumor even after multiple biopsies.

Advexin is currently being evaluated by the Food and Drug Administration for use in recurrent head and neck cancers. In Europe, approval is pending for its use on a rare inherited cancer, Li-Fraumeni syndrome, in which sufferers are born with defective p53 genes.

Last November, Advexin’s maker, the Austin, Texas-based Introgen Therapeutics Inc., entered into an alliance with Colgate-Palmolive Co. in New York to incorporate the gene therapy into mouthwashes and gels to treat and prevent oral cancers. The mouthwash is now in the early stages of clinical tests for the prevention of oral cancers in high-risk patients.


“This is a glimpse of the future application of these agents,” says David Nance, chief executive of Introgen. “To prevent or reverse cancer in its earliest stages.”