Genetically modified Salmonella can kill cancer cells, suggests new research published in mBio, an American Society for Microbiology. one particular strain of salmonella found to be most effective at killing cancer cells and shrinking tumors, and also not toxic.
For years, researchers have known that certain strains of bacteria, including Salmonella enterica, can kill cancer cells. Specifically Salmonella enterica Serovar Typhimurium has been shown to not only colonize solid tumors, but also to exhibit an intrinsic antitumor effect.
However, in order to use Salmonella as a weapon against cancer in humans, researchers must find a balance between allowing it to kill the cancer and be safe for the patient. The bacteria, commonly known for causing severe food poisoning, can lead to sepsis and death in humans.
“There has long been interest in using genetically engineered microbes to target and destroy cells within solid tumors. I think this study goes a significant way in developing some strategies that will help in the overall means of using Salmonella as part of a cancer therapy,” said Roy Curtiss, III, PhD, who was involved with the research.
In the new study, the researchers focused on modifying the lipopolysaccharide structure (LPS) of the Salmonella strain to make the bug less toxic. LPS, found in the outer membrane of bacteria, is one of the major inducers of sepsis, a life-threatening infection.
The scientists utilised genetic engineering to remove genes involved in the synthesis of the LPS, and then tested various modified Salmonella strains to see how they performed in test tube studies with human cancer cells and in tumor bearing mice.
Researchers identified a particular mutant strain that was the most effective at killing cancer cells and shrinking tumors, and also unable to cause disease. However, this mutant strain was less able to colonize the tumors, although being most effective in killing tumor cells when getting there.
To address this problem, the researchers then added another genetic modification, an inducible arabinose promoter. The modification allowed the Salmonella to be injected in the mouse in a form that would not harm normal, healthy cells, was effective at colonizing tumors, and after entering cancer cells, would turn toxic.
"This transition from a benign, invasive Salmonella that doesn't hurt normal cells to the toxic type occurs very rapidly (time wise) in the tumor due to the very rapid growth and cell division that occurs when Salmonella enters a tumor," said Dr. Curtiss. In a normal cell, Salmonella grows very slowly, dividing once or twice in a 24-hour period, but in a tumor, the bacteria divide every hour.
According to Dr. Curtiss, the investigational therapy would probably be used in conjunction with chemotherapy and radiation therapy, once it gets to human trials.
