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Polio virus hybrid kills brain tumors

Monday, 21 May 2001 19:24 (ET)

ORLANDO, Fla. May 21 (UPI) -- Tests on mice show that genetically crossing the virus that causes the common cold with the one that causes polio can kill one of the deadliest and most common types of brain tumors, researchers said Monday.

"We took a little piece of the gene from the rhinovirus, the virus that causes colds, and put it into the polio virus genome, creating a variant of the polio virus that no longer has the ability to replicate itself and cause disease," Dr. Mathias Gromeier, with Duke University Medical Center in Raleigh, N.C., told United Press International.

"Because the two viruses are very similar, the result was especially lethal to malignant human glioma cells without any risk of polio," he said. Gromeier presented his findings at the annual meeting of the American Society of Microbiology.

Malignant glioma is a deadly form of brain cancer that strikes about 12,000 people each year in the United States, disproportionately affecting young children and the elderly. The cancer does not respond well to chemotherapy, radiation treatment or surgery, so finding ways to kill glioma tumors using such targeted treatment offers the promise of a better prognosis for patients facing an otherwise bleak future, Gromeier said.

"We have a virus that no longer causes disease but grows very well in brain tumors. Once we inject it into the tumors, it kills them with no side effects," he said.

The genetically tweaked hybrid polio/rhinovirus also may work against other forms of cancer, including colon and lung cancer, although unlike brain cancer, these can spread to other parts of the body, making such treatment more difficult, he noted.

Gromeier and his team have started initial toxicity and safety tests required by the Food and Drug Administration before human clinical trials can be conducted. If all goes well, the procedure could be available in about two years, he said.

Dr. Phil Gutin, an expert on brain tumor treatment at Memorial Sloan-Kettering Cancer Center in New York City, said the technique is an entirely new approach to killing cancer and is not without controversy. "Poliovirus is one sort of virus not being used for conventional gene therapy, with the transfection of genetic material into tumor cells, but as an oncolytic virus to spread through tissue and kill tumor cells directly," Gutin said.

"While it has considerable potency against brain tumor cells in experimental animal systems, it can only be tested in humans with the FDA's blessing. Obviously, there is considerable fear about this sort of virus, but is has been rendered non-pathogenic by changing its structure slightly from the wild type poliovirus."

Gutin, chief of neurosurgery at Sloan-Kettering, said brain tumors are particularly challenging because of their resistance to therapy, their location in a critical organ and the fact they are so invasive. Other oncolytic viruses are being tested or are on the horizon, he added.

Other researchers have noted Gromeier's technique may not be entirely effective in killing the brain tumor. In an editorial on an earlier study by Gromeier, published last June in the Proceedings of the National Academy of Sciences, Dr. Eric Holland said while encouraging, all strategies for killing gliomas with viruses or viral vectors "are hindered by the need for the tumor cells to undergo infection."

Holland, who now also is a neurosurgeon at Memorial Sloan-Kettering, wrote: "Given the genomic instability and heterogeneity of gene expression within (gliomas), it is likely that many cells within each tumor will be inherently resistant to viral infection because of lack of expression of the viral receptor."

(Reported by UPI Medical Writer Kurt Samson in Washington.)

Copyright 2001 by United Press International.

-- Swissrose (cellier3@mindspring.com), May 21, 2001