Defanged Bugs May Take on Tumors

The mention of Salmonella may evoke stomach-churning thoughts of burgers gone bad, but the food-poisoning bugs actually have potential to do good: a curious knack for battling tumors. Still, injecting Salmonella into the bloodstream of cancer patients was never an option, because that would cause deadly septic shock. Now a bit of genetic engineering, reported in the current issue of Nature Biotechnology, seems to have tamed the bugs' virulence enough to raise the prospect of cancer therapy.

For some mysterious reason, Salmonella seek out and multiply in tumor cells. When a mouse with melanoma is infected with specially altered Salmonella strains, the bugs ignore their usual target (the liver) and head straight for the tumor--dramatically slowing its growth. Researchers are eager to test this talent in human tumors, but a critical stumbling block remains: Salmonella infection in humans incites abnormally high levels of TNF-a, a molecule that causes inflammation in a normal immune response, damaging cells and leading to organ failure.

Now David Bermudes, a microbiologist at Vion Pharmaceuticals in New Haven, Connecticut, has found a way to ameliorate such deadly side effects without compromising the bacteria's tumor-fighting strength. His team mutated the gene encoding a protein that puts the finishing touches on Lipid A, a molecule in the bacterial cell wall that triggers inflammation. Unable to fully assemble their Lipid A, the bacteria are much less toxic. The team could then inject many fold more bacteria into the animals without sparking an adverse immune response, while still squelching tumor growth to as little as 6% of that in untreated animals. "We took something that was therapy for mice and made it into something that can be used for humans," says Bermudes. The results are so promising, Bermudes says, that Vion is planning to begin human clinical trials this year.

The study is thorough and well-done, says Richard Darveau, a microbiologist at the University of Washington in Seattle. But he cautions it's too soon to tell if the bacteria is actually engaging in direct combat with the tumor cells.