An important article in The Scientist recently quoted Neil Forbes, chemical engineering, commenting on how researchers are using probiotics and microbes to detect, diagnose, and treat cancer, a subject closely associated with Forbes’ own research. The article was about researchers at MIT and the University of California, San Diego, who have programmed a probiotic Escherichia coli strain to detect cancer metastases in the liver. The team used these bacteria, also described in the May 27 issue of Science Translational Medicine, to detect cancer in mice.
“This is a wonderful example of using synthetic biology for a medical goal,” said Forbes, who is working independently to program microbes as cancer diagnostics and therapies.
For more than 12 years, Forbes has been working on non-pathogenic Salmonella bacteria that can use their own self-propulsion system to venture deep into tumors and deliver cancer-destroying agents, all without causing the vicious side effects of many chemotherapy treatments.
In The Scientist article the researchers describe how they engineered the microbes to express high levels of β-galactosidase — an enzyme that helps E. coli digest lactose. They then injected the animals with LuGal, a conjugate of the bioluminescent protein luciferin and galactose. The enzyme β-galactosidase cleaves LuGal, freeing the luciferin. The molecules are then excreted in mouse urine. When the researchers add luciferase to the urine, its interaction with luciferin releases light. The researchers demonstrated that, by measuring how brightly the urine glowed, they could determine whether mice had cancer in their livers.
Forbes recently received a five-year, $1.56-million grant from the National Institutes of Health (NIH) to engineer what he calls “super-safe Salmonella bacteria” to act as Trojan Horses and deliver cancer-killing agents directly into tumors. His Salmonella vectors are designed to steal into cancer tumors, interrupt essential cell processes there, destroy cancer cells, eliminate cancer stems cells, reduce tumor volume, and block the formation of metastases.
Forbes and his graduate student Miaomin Zhang also recently published the cover article of the Journal of Controlled Release (vol 199, February 10, 2015), which has an impact factor of 7.8. The title of the article is "Trg-deficient Salmonella colonize quiescent tumor regions by exclusively penetrating or proliferating."