Tamed Herpes Destroys Cancer Cells

Scientists have concocted a virus that sneaks toxins into cancer cells. The technique, described in the current issue of Nature Biotechnology, could be particularly useful for decimating residual cancer cells after a tumor is surgically removed.

Viruses are a natural courier for drugs, because they easily slip inside cells. Antonio Chiocca, a neuro-oncologist at Massachusetts General Hospital in Boston, thought he might find a way to tell a virus to damage only cancer cells. Chiocca took the herpes simplex virus and disabled it by deleting the gene for ribonucleotide reductase, an enzyme necessary for the virus to replicate. Because cancer cells churn out abnormally high levels of ribonucleotide reductase, Chiocca reasoned that the virus would only reproduce in and burst out of cancer cells. To make the tumor-targeting virus more deadly, Chiocca armed it with a second weapon--the gene for CYP2B1, a protein that activates a drug called cyclophosphamide (CPA).

When Chiocca and his colleagues unleashed the modified virus on cultured cancer cells, 60% survived. When they bathed the infected cells in CPA, only 10% survived. The group then injected the virus and CPA into five mice carrying human brain tumors. After 3 weeks, four of five tumors disappeared. In five mice injected only with the virus, one tumor regressed.

After surgery to remove a tumor, the virus-CPA cocktail could be used to kill off malingering cancer cells, says team member Richard Chunga: "This way, we can be sure to get the few cells that are left." One advantage of the approach, adds Michael Blaese, chief of the gene therapy branch of the National Human Genome Research Institute in Bethesda, Maryland, is that the virus can get many tumor cells that surgery misses. However, Blaese points out, "the immune system is not just sitting there scratching its chin." It can eliminate the virus in a few weeks, he says, and could react even faster to repeated treatments--thus diminishing the treatment's value.