Salmonella vector overcomes an obstacle

A year ago, scientists at Yale and Vion Pharmaceuticals reported success in experiments that used a modified salmonella bacterium as a vector to attack tumors in mice. Now the researchers have found a way to reduce the risk of potentially fatal septic shock in humans, making the mutated salmonella a candidate for cancer therapy. “You can eliminate the main culprit that induces septic shock from bacteria,” said David Bermudes, Ph.D., assistant professor (adjunct) of medicine and associate director of biology at Vion, which is funding the research. Bermudes, K. Brooks Low, Ph.D., and John M. Pawelek, Ph.D., who have collaborated on the salmonella experiments, removed from the bacterium a gene essential to the biosynthesis of lipid A, or endotoxin, which induces septic shock.Their findings were published in the January issue of Nature Biotechnology.

The mutated salmonella, tested in mice and pigs for safety, has been shown to reduce tumor growth in mice by more than 90 percent. Injected directly into the blood stream, the bacterium suppresses, but does not completely eliminate, tumors through a process the scientists have yet to decipher. Phase I clinical trials are expected to begin this year.