Food poisoning may turn your stomach, but researchers have found a way to convert the troublesome bacteria into heroes. A new study suggests that genetically modified Salmonella can inject cancer cells with proteins that make tumors easier to fight.
Salmonella bacteria are the most common cause of food borne illness in the United States, nauseating nearly 40,000 people each year. Key to Salmonella's success is a syringelike protein called a Type III Secretion Apparatus that injects toxic proteins into any other cells with which it crosses paths. Fortunately, our immune system quickly hones in on markers unique to the bacteria's surface, clearing the invasion in a matter of days. A more dangerous enemy--the cancer cell--is far harder to catch. That's because its surface markers are the same as those seen in the body's normal cells.
Immunologists Hiroyoshi Nishikawa and Sacha Gnjatic of the Ludwig Institute for Cancer Research in New York City, molecular biologist Jorge Galan of Yale University, and colleagues wanted to see if they could somehow use Salmonella's "syringe" to inject cancer cells with proteins that the body could detect. First, they stripped the bacteria of genes that code for proteins that make animals sick. Then, they engineered the syringe to inject a protein called NY-ESO-1. The protein is not normally found in healthy cells, and therefore it should raise a red flag for the immune system.
To see if the bacteria had become cancer fighters, the team vaccinated mice against NY-ESO-1 to boost their response to the protein. Then the researchers injected the modified Salmonella into the tumors. Analysis of tumors revealed that individual tumor cells contained NY-ESO-1, indicating that they had been successfully injected by the Salmonella's syringes. Over 3 weeks, each of five mice given the modified Salmonella had their tumors shrink from 400 millimeters in diameter to less than 10 millimeters. In contrast, tumors got bigger in control mice given regular Salmonella, the team reports online today in the Journal of Clinical Investigation.
Using Salmonella to fight cancer "is a novel and exciting concept," says Robert Schreiber, a tumor immunologist at Washington University Medical School in St. Louis, Missouri. "Perhaps the most provocative finding," he says, is that scientists can chose which protein they want to inject into the tumor and can therefore guide the immune response. But Elizabeth Jaffee, an oncologist at Johns Hopkins Medical Institute in Baltimore, Maryland, says the research would be more clinically relevant if NY-ESO-1 existed in the host over longer periods of time before being experimentally tested. If the mice develop a tolerance to NY-ESO-1 over time, the therapy may only be a temporary fix, she says.
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