When Bad Bugs Go Good

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Forty years later, scientists know a lot more about genes and proteins and how to target microbes so that they home in on one particular kind of cell--a cancer of the ovary, for example, or a tumor in the throat. They have also learned to affix molecular tracking devices to a microbe to ensure that when let loose in the body, it doesn't deviate from its therapeutic mission.

The ideal microbial ally, say scientists, is one that already infects humans and yet can be easily controlled with antibiotics or antiviral medications should something go awry. For his research, Russell likes the measles virus, in particular, the modified strain of the virus used for more than five decades in the measles vaccine. That weakened form has a special fondness for tumors, lured there by a protein expressed in copious quantities on the surface of malignant cells. As part of an ongoing trial in ovarian-cancer patients, Russell's colleague Dr. Eva Galanis constructed a measles virus that could also churn out a protein that can be picked up in the blood, allowing the investigators to measure how well the virus is working. The final results of their trial won't be available for another year or so, but the strategy appears to be working. Russell and Galanis are also targeting brain tumors and have designed a measles virus that recognizes a mutation often found in brain-tumor cells but never in normal ones.

Of course, a virus has to reach its target to destroy it, and that means surviving the defensive armies of a formidable opponent: the immune system. "Blood is a pretty hostile environment for the viruses," notes Russell. "The name of the game is to dodge the immune defenses for a few hours and give the viruses enough time before the immune system gets in and stops them." His group is perfecting two approaches: 1) temporarily distracting the immune system with drugs that suppress it and 2) cloaking the virus in a protective protein coat that renders it invisible to immune cells.

Other bug-based therapies for cancer take advantage of the body's natural response to invaders. To this end, scientists at the Texas Medical Center have enlisted the aid of the Epstein-Barr virus (EBV). More than 95% of the population is infected with EBV, a usually benign microbe that sequesters itself in the immune system's B cells. Like any other cellbound virus, EBV doesn't remain dormant for long, dividing furiously and emerging in runaway viral mobs. But unlike most other viruses, EBV is quickly eliminated by the vigilant immune system's killer T cells.

The Texas scientists wondered whether they could take advantage of that existing defense system and use the transformed B cells as cancer alarm bells. By customizing EBV-infected B cells with proteins specific to certain cancers, they could grow killer T cells in the lab that are trained to fight those specialized B cells. The T cells would then be able to find and destroy malignant cells as if they were just another cell infected with a virus.