Turning Viruses Into Allies Against Cancer with Radiovirotherapy.

To most, the mere mention of the word "virus" stirs up memories of pain, fever and varying levels of suffering. But in recent years, scientists have been trying to turn these long-time medical foes into allies in the fight against cancer.

Through genetic engineering, viruses are being reprogrammed to take advantage of their natural abilities to infiltrate, commandeer, replicate and destroy, but only in tumor cells and not surrounding healthy tissue.

Several of these "oncolytic" (cancer-killing) viruses are in varying stages of development, including modifications of the virus that causes measles and another, the herpes simplex virus, responsible for those lip blisters known as cold sores.

In a study presented this week at the 96th meeting of the American Association for Cancer Research (AACR), researchers describe their latest studies with their engineered versions of these viruses.

Engineered Measles Virus Seeks Out and Destroys Liver Cancer Cells: Abstract LB-297

A weakened measles virus, modified with a protein that normally takes up iodine in the thyroid gland, is being studied to treat human liver cancer cells grafted in an animal model.

Scientists at the Mayo Clinic in Rochester, MN, reported that the engineered virus seeks out and destroys liver cancer cells, leaving surrounding healthy tissue in tact.

The iodine "transport" protein attached to the virus acts as a kind of homing beacon for radioactive iodine, providing a second line of attack against the cancer cells, technically known as radiovirotherapy.

"These results clearly demonstrate the high potential of this modified virus to serve as a novel vector for cancer gene therapy of hepatocellular carcinoma," said Boris Blechacz, MD, a research fellow in the Molecular Medicine Program at the Mayo Clinic and the study's lead investigator.

Liver cancer is one of the leading causes of cancer death worldwide, causing nearly a million deaths per year. Despite a variety of differing treatment approaches, its prognosis remains poor with a median survival of about 10 months following diagnosis. For this reason, scientists are anxious to find novel methods that could improve short- and long-term survival from this disease.

"The attenuated vaccine strain of measles virus is an oncolytic virus which has shown antitumor activity and tumor-selectivity in a variety of different tumor models," said Blechacz. "But its potential in primary liver tumors has never been evaluated."

In the first part of their study, the scientists studied the impact of their modified measles virus (MV-Edm) in liver cancer cell lines from human patients. Analysis of liver cancer cells removed from patients shows that these cells contain large amounts of the natural receptor for the measles virus, CD46. Overexpression of this receptor thus makes liver cancer cells ideal targets for the measles virus. The results confirmed widespread infectivity, toxicity and destruction among these cells, probably through apoptosis or programmed cell death.

When the modified virus was injected directly into human liver cancer cells grafted onto laboratory mice, scientists observed significant prolongation of life; complete regression was achieved in up to one-third of the treated mice.

During the second phase of their study, the scientists attached the iodine "symporter" protein to the MV-Edm and injected the newly engineered virus intravenously into the mice carrying the human liver cancer cells.

"Intravenous treatment with this combination followed by injection of radioactive iodine into the mice bearing the human hepatocellular cancer cells resulted in high uptake of the radioactive iodine at the tumor site," said Blechacz. "This provides the possibility of enhancing the therapeutic effect by cotreatment with therapeutic radioactive iodine."

Future studies should help scientists evaluate the efficacy and optimal delivery system of their radiovirotherapy vector.

"We expect this work will take another two years before this technology will be available for testing in patient studies," said Blechacz.