ROANOKE TIMES
Copyright (c) 1996, Roanoke Times
DATE: Friday, October 18, 1996 TAG: 9610180064
SECTION: NATIONAL/INTERNATIONAL PAGE: A-1 EDITION: METRO
DATELINE: WASHINGTON
SOURCE: Associated Press
WHEN GENETICALLY altered, the adenovirus kills human cancer tumors implanted in mice.
Reshuffling the genes of an ordinary cold virus turns it into a cancer-killing smart bomb able to seek out and destroy tumor cells, researchers report. The therapy is already being tested on human beings.
A mutated version of adenovirus, one of a number of viruses that cause the common cold, was shown in mouse studies to attack and kill human cancer cells that lack a gene called P53.
About half of all human cancers have a defective or missing P53 gene.
``The mutated virus takes over and turns the [cancer] cell into a factory to make more virus,'' said Frank McCormick, a researcher at Onyx Pharmaceuticals in Richmond, Calif. ``After a day or two, the cell is killed and it releases a whole bunch of new virus, which then infect neighboring cancer cells.''
About 60 percent of human tumors grown in laboratory mice melted away after being injected with the mutated adenovirus, said McCormick, lead author of a study published today in the journal Science.
Dr. Bert Vogelstein, a Johns Hopkins University researcher who first discovered that an altered or missing P53 gene can lead to cancer, called the report exciting ``because it exploits an alteration that is present in many different cancers.''
The altered virus' true cancer-fighting ability won't be known until human trials are done, Vogelstein noted.
The virus affected only the cancer cells, working rather like a smart bomb that attacks specific targets without damaging nearby structures.
``This doesn't necessarily say that this same thing will happen in human patients,'' McCormick noted. The adenovirus often will not attack mouse cells. Also, since the mice used in the study lack an immune system, the virus could spread unchallenged.
A normal P53 gene suppresses cancer by detecting abnormal DNA when a cell is dividing. If the DNA is abnormal, P53 either stops the division or kills the cell. That also can block the reproduction of viruses within the cell.
Many types of human cancers have defective or missing P53, and this allows the tumor cells to survive and proliferate wildly.
A normal adenovirus causes mild upper-respiratory infections by invading a cell and making a protein that renders P53 inactive. That enables the virus to take over the cell, turn it into a virus-making factory and eventually kill the cell, releasing into the blood stream the new viral particles.
The alteration's effect, McCormick said, is to make the virus unable to replicate efficiently in normal cells, which have P53, but able to thrive in cancer cells that lack the gene.
As a result, he said, the virus uses cancer cells to make more virus and then kills the cells. The new viral particles then infect other cancer cells.
To test the altered virus, the researchers injected human cancer cells into so-called nude mice, a lab species that grows human tumors because it lacks an immune system.
Once the human cancers were established, the researchers injected the tumors with the altered adenovirus.
``In 60 percent [of the mice], we see the complete removal of the tumor,'' McCormick said. ``We see the virus spread inside the tumor until the inside is gone and then only scar tissue is left.''
LENGTH: Medium: 67 linesby CNB