The results of a study using a modified adenovirus, which is often responsible for garden-variety sniffles and sneezing, are so promising that the National Cancer Institute plans to produce a version of the virus that it could test in humans as early as next year.
Other experts, however, urge caution when interpreting the findings.
"This is something that is interesting, that has potential, but it has a long way to go from this type of experiment into saying that this is going to have a definite application for the treatment of patients," says Dr. Len Lichtenfeld, a spokesman for the Cancer Control Science Division of the American Cancer Society. "Scientists and researchers have been very interested in the concept of adapting viruses to cancer treatment and with all of the excitement around them, we still don't have a definite example of something that's been clinically effective."
The findings appear in the May 7 issue of the Journal of the National Cancer Institute.
The targeted virus therapy appears to have cured mice of malignant gliomas, extremely aggressive brain tumors that affect both adults and children and which have no known treatment. "Once a tumor becomes malignant, survival with everything we do is 12 to 18 months," says Dr. Kevin Lillehei, a professor of neurosurgery and director of neuro-oncology at University of Colorado Health Sciences Center in Denver.
Researchers had already known that an Achilles heel of cancer cells is the retinoblastoma (Rb) protein. In normal cells, the Rb protein acts as a brake on cell division. When it is absent, however, cells start proliferating furiously to form a tumor.
Years ago, Dr. Juan Fueyo, lead author of the paper and an assistant professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center in Houston, and his wife, Candelaria Gomez-Manzano, who is also an author on this paper, constructed an adenovirus that would replicate itself and destroy cells that lacked the Rb protein. This virus was called Delta-24.
But there was a problem. Not all tumors had receptors or "doors" that would allow Delta-24 to enter. Fueyo and Gomez-Manzano then modified the adenovirus in collaboration with the University of Alabama at Birmingham so it could latch on to integrins on the outside of the cancer cells. "We found an open door for the virus in the cancer cells," Fueyo explains. The modified virus is called Delta-24-RGD.
For this study, Fueyo and his colleagues injected Delta-24-RGD directly into the brains of mice with malignant gliomas and compared those results with mice who had received either Delta-24 or a placebo.
The mice who received a placebo lived a mean of 19 days, while 15 percent of those who received Delta-24 lived to the end of the experiment (more than four months) and were considered cured.
However, 60 percent of the mice who received Delta-24-RGD survived to 100 days and were considered cured. In fact, the treated mice never died on their own but were "sacrificed electively" to investigate what had happened to the tumor. No tumors were detected; rather, empty cavities and scar tissue were found in their place.
"It's really true that the injection to the brain tumors in this model cured the animal," Fueyo says. "It's amazing."
This success may not be enough, however. "It's exciting but very preliminary, the reason being delivery," Lillehei cautions. "It's a small model; you can diffuse the tumor relatively well. But when you get into the brains of humans, it's a large area, and can you deliver the virus adequately to really slow down the growth?"
Another potential problem is immunity. Since so many people have had the common cold, they may have developed antibodies to the adenovirus, enabling their bodies to beat it back.
The other unknown is whether this therapy will work on other cancers. The virus will infect other cancer cells, Fueyo says, but gliomas are unique in that they do not spread, or metastasize. "I have no experience with the systemic delivery that might be required for [metastasized] cancers," he says.
One of the advantages of the virus in treating gliomas is that it is easily delivered through a small hole in the skull of the patient, which is not considered major surgery.