Neil Forbes of the Chemical Engineering Department was interviewed by local public radio station WFCR on December 11 about the delivery and trigger system he has developed to place TRAIL, a cancer-fighting protein, directly into solid tumors and to activate it on cue. Forbes engineered a non-toxic kind of Salmonella bacteria that can use its own self-propulsion system to venture deep into tumors and manufacture the powerful anti-cancer drug. In laboratory testing, the new therapy, when combined with radiation treatment, delivered what Forbes calls a “double whammy” that swelled the 30-day survival rate of mice with breast cancer from 0 percent to 100 percent.
The experiments, conducted in the Pioneer Valley Life Sciences Institute at Baystate Medical Center in Springfield, Massachussetts, were reported in a recent issue of the British Journal of Cancer. Forbes told WFCR that he had designed a “troop transport” of sorts, which would be controllable in location and time, to attack tumor cells directly so that chemotherapy patients suffer few or no bad side-effects.
The importance of the journal article is that it describes laboratory testing on the first bacterial delivery system ever used to transport and manufacture the anti-cancer drug TRAIL, a murine TNF-related apoptosis-inducing ligand.
“It sounds like science fiction, doesn’t it?” Forbes said in a recent press release that inspired his WFCR appearance. “But Salmonella bacteria, in effect, are each little robots that can swim wherever they want. They have propellers in the form of flagella, they have sensors so they can tell where they’re going, and they’re also little chemical factories. So what we’re doing as engineers is controlling where they go, what chemical we want them to make, and when they make it.”
Using Salmonella to attack cancer tumors is a technique that has been tried with only moderate success since the sixties. But Forbes’ work with Salmonella is introducing a radical improvement called “targeted intra-tumoral therapeutic delivery,” or sending the bacteria into parts of the tumor that are currently beyond the reach of conventional cancer therapies. Now Forbes has engineered a non-pathogenic strain of Salmonella typhimurium to travel specifically to tumors and produce TRAIL when “turned on” by radiation therapy.