A common cold virus has been transformed into a treatment for prostate cancer -- the second biggest cancer killer among Western men after lung cancer.
Scientists at the Johns Hopkins Oncology Center in Baltimore and a Californian biotech company called Calydon have created a mutant strain of the common cold virus that attacks only prostate cells.
The virus can penetrate any cell but becomes active only in those producing prostate specific antigen, a protein involved in the production of semen and found almost exclusively in the prostate.
To create the new virus, Calydon researchers first identified the human gene that makes PSA and then found the regulatory part of it, which ensures that PSA is only produced by cells in the prostate gland.
They then put this regulator sequence into the viral genome, adding it to a larger gene that is critical for viral replication. As a result, when the virus finds itself in a prostate cell, the PSA regulator turns on the viral replication gene, making the virus reproduce and destroying prostate tissue.
The virus destroys normal prostate tissue as well as cancerous cells. But the prostate gland is not essential for fertility or potency, and other treatments such as surgery, chemotherapy and radiation also destroy the gland.
If the virus finds itself in a non-PSA-producing cell, it sits there quietly until the cell's normal metabolism degrades it, says Daniel Henderson of Calydon.
In studies of prostate cancers in mice, a single injection of the virus directly into the gland was found to shrink tumors dramatically within six weeks, without side effects.
Results reported in this month's issue of Cancer Research show that on average, tumors were reduced to 16 percent of their original size. Human clinical trials are due to start soon. Researchers hope eventually to deliver the virus intravenously so that it can hunt down prostate cancer metastases hidden throughout the body.
The Calydon virus has been found replicating in some cells taken from tissues that don't produce PSA, but Jonathan Simons, one of the Johns Hopkins researchers, says this is unlikely to harm patients. "It's more likely that the immune system will get rid of these," he says.
A bigger problem arises from the large doses of virus that are required, in order to infect as many cells as possible in the prostate. Most people have been exposed to common colds at some time, so the immune system is primed to get rid of the viruses that cause them.
Frank McCormick, a researcher at the University of California at San Francisco, who is working on similar viruses, says the danger of side effects is linked to how specialized the virus is.
McCormick is working on viruses that have been engineered to selectively infect cancer cells lacking a tumor-suppressing protein called p53.
Pub Date: 7/27/97