Neil Forbes of the University of Massachusetts Amherst has received a four-year grant of more than $1 million from the National Institutes of Health to research killing cancer tumors with Salmonella bacteria.
Forbes turns the bacteria into tiny terminator robots that use their own flagella to venture deep into tumors where conventional chemotherapy can't reach. Once in place, the bacteria manufacture drugs that trigger cancer cells to kill themselves.
“When we get the Salmonella bacteria into the part of the tumor where we want them to be, we've programmed them to go ape,” says Forbes. “We have the bacteria release a drug to trigger a receptor in cancer cells called the “death receptor,” which induces cancer cells to kill themselves. We've already done this in the lab. We've done this successfully in cancerous mice, and it dramatically increases their survival rate.”
Normally, mice with tumors all die within 30 days. After receiving this bacterial system and getting a dose of radiation, all the mice in Forbes' lab tests survived beyond the 30 days, which could potentially translate into many months or years in people.
“It sounds like science fiction, doesn't it?” says Forbes, an assistant professor in the chemical engineering department. “But Salmonella are little robots that can swim wherever they want. They have propellers in the form of flagella, they have sensors to tell them where they are going and they are also little chemical factories. What we do as engineers is to control where they go, what chemical we want them to make, and when they make it.”
Using bacteria to attack cancer tumors has been tried with only moderate success for decades. But Forbes' work with Salmonella is introducing a radical improvement called “targeted intratumoral therapeutic delivery,” which sends the bacteria into parts of the tumor that are currently beyond the reach of conventional therapies. This could translate into individualized doses of chemotherapy for human cancer patients, make therapy more specific and effective, give people smaller doses of chemicals while they are being treated and cut down on patient mortality.
The basic problem being addressed by Forbes is that some regions in any cancer tumor are impossible to reach with current chemotherapy drugs. Drug access to the tissue in any tumor is limited by the distribution of its blood vessels. Tissue located farthest from its surrounding blood vessels is the hardest for drugs to reach because the vessels act as their chemical highways into the tumor. Every tumor has a different distribution of blood vessels, depending on the nature of the tumor and the patient's genetic makeup.