Fighting cancer with bacteria?

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Salmonella Bacteria Turned Into Cancer Fighting Robots

Libraries Medical News		Keywords CANCER, TUMORS, CHEMOTHERAPY, SALMONELLA, INTRATUMORAL THERAPEUTIC DELIVERY
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Description Salmonella bacteria can be turned into tiny terminator robots that venture deep into cancerous tumors where conventional chemotherapy can't reach. Once in place, the bacteria manufacture drugs that destroy cancer cells. This could translate chemotherapy that is more specific, more effective and easier on patients.

Newswise - 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.

"Think of the region between blood vessels as a sponge," explains Forbes. "The particles from a therapeutic drug tend to accumulate around the outer portions of the sponge, nearest the blood vessels, and not penetrate to the interior."

That's where an unlikely hero, the Salmonella bacterium, comes in. Unlike drugs (which are not alive), Salmonella can take energy from their environment and can "swim" wherever they please. They have their own outboard motors called flagella, and can travel where they want in a tumor, regardless of blood vessels. Forbes' concept is to use special Salmonella disarmed of their toxicity and fix them with drug payloads so they can swim into these hard-to-reach regions of the tumor and kill the cancer cells there.

"The bacteria, as far as I can tell, are the only therapy that can penetrate deep into tissue, far beyond where blood vessels reach," says Forbes.

Bacteria naturally seek out dead tissue for food by using sensors that home in on chemicals such as ribose, given off by dying cells. But Forbes doesn't want his Salmonella robots going to the dead cancer cells already killed off by chemotherapy. He wants them penetrating to the slow-growing, but live, cancer cells that current therapy can't touch. So his solution is to remove the ribose sensor from Salmonella.

"By knocking out the ribose receptor, we can keep the bacteria away from dead cells, where we don't need them to go, but get them to travel into slow-growing cells located in hard-to-reach tissue far from blood vessels; the regions currently beyond our therapeutic treatment," says Forbes.

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Using an innovative method to control the movement of Escherichia coli in a chemical environment, Emory University scientists have opened the door to powerful new opportunities in drug delivery, environmental cleanup and synthetic biology.

Their findings are published online in the Journal of the American Chemical Society and will be published in a future print issue.

Justin Gallivan, PhD, assistant professor of chemistry, and graduate student Shana Topp successfully reprogrammed E. coli's chemo-navigational system to detect, follow and precisely localize to specific chemical signals. In doing so, the scientists exploited E. coli's natural chemotaxis, a microbe's ability to move toward specific chemicals in its environment.

"Equipping bacteria with a way to degrade pollutants, synthesize and release therapeutics, or transport chemicals with an ability to localize to a specific chemical signal would open new frontiers in environmental cleanup, drug delivery and synthetic biology," says Dr. Gallivan.

The researchers equipped E. coli with a "riboswitch," a segment of RNA that changes shape when bound to certain small target molecules, which can then turn genes on or off. Dr. Gallivan and Topp believe that the riboswitch can be used to equip other types of self-propelled bacteria with "chemo-navigation" systems to move them toward desired targets.

Chemotactic bacteria navigate chemical environments by coupling their information-processing capabilities to powerful, tiny molecular motors that propel the cells forward.

Researchers have long envisioned reprogramming bacteria so that microbes capable of synthesizing an anti-cancer drug, for instance, can be used to target diseased cells while sparing healthy cells of side effects. Likewise, scientists are researching ways to use bacteria to clean up oil spills or remove other pollutants from soil, water and wastewater.

"This new ability to equip motile bacteria with a precise and tunable chemo-navigation system will greatly enhance the impressive arsenal of natural and engineered cell behaviors," says Dr. Gallivan

Husband11

That's a brilliant strategy.  Thanks for posting it up.