Virus that targets and kills glioblastoma

May 11 2005

Yale School of Medicine scientists have identified a virus that targets and kills glioblastoma, a deadly type of human brain tumor resistant to current medical or surgical treatment, according to a study published as the cover article in the Journal of Virology.

“Malignant glioblastomas are the most common primary brain tumors, causing more than 13,000 deaths each year,” said Anthony van den Pol, professor of neurosurgery at Yale School of Medicine and senior author of the study. “There are currently no known medical or surgical approaches that constitute an effective cure for glioblastoma, and most patients diagnosed with this type of brain tumor live less than a year.”

Van den Pol’s team put nine different DNA and RNA viruses through a series of tests to determine which infect, slow down, or kill brain tumor cells. The researchers then took the viruses that were most effective at killing tumor cells, cultivated viruses for many generations on brain tumor cells, and selected virus clones with improved tumor–killing capacity and reduced capacity to infect non–tumor cells. The winning candidate was a strain of vesicular stomatitis virus (VSV) that replicates quickly. Whereas humans and other mammals use DNA to carry their genetic code, the viral genome of VSV is encoded by RNA, van den Pol said.

To track the virus as it invaded tumor cells, a recombinant VSV was used that contained a reporter gene isolated from jellyfish that turns infected tumor cells green.

Virus particles that cannot replicate have been used to kill cancer cells, but they can only infect a relatively small number of tumor cells. Van den Pol’s group theorized that if the replication–competent virus encounters a tumor cell, it will infect the cell, replicate in the tumor cell, and, as the tumor cells die, more viruses will be released that then target more tumor cells. Van den Pol said the current project is the first stage and more work is needed to ensure the safety of the virus before it can be considered for use in clinical trials.

The first author was Guido Wollmann, postdoctoral associate. Peter Tattersall, professor of genetics and laboratory medicine, was co–author. The study was funded by the National Institutes of Health and the National Cancer Institute.