A new strategy uses genetically programmed bacteria to detect when enough of them have gathered inside a tumor – then switch on survival mechanisms at just the right moment.
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Researchers are exploring an unconventional cancer treatment that uses engineered bacteria to target the unique, oxygen-free environments inside tumors.
A research team led by the University of Waterloo is developing a new way to treat cancer by engineering bacteria that can consume tumors from the inside.
“Bacteria spores enter the tumor, finding an environment where there are lots of nutrients and no oxygen, which this organism prefers, and so it starts eating those nutrients and growing in size,” said Dr. Marc Aucoin, a chemical engineering professor at Waterloo. “So, we are now colonizing that central space, and the bacterium is essentially ridding the body of the tumor.”
The approach relies on Clostridium sporogenes, a bacterium commonly found in soil that can grow only in completely oxygen-free conditions.
The center of a solid cancerous tumor is made up of dead cells and lacks oxygen, creating an ideal environment for this bacterium to thrive and multiply.
Credit: University of Waterloo
However, there is a key limitation. As the bacteria spread toward the outer layers of tumors, they encounter small amounts of oxygen. This exposure causes them to die before they can fully eliminate the tumor.
To overcome this challenge, researchers introduced a gene from a related bacterium that is better able to tolerate oxygen. This change allows the engineered bacteria to survive longer near the tumor’s outer regions.
However, there is a key limitation. As the bacteria spread toward the outer layers of tumors, they encounter small amounts of oxygen. This exposure causes them to die before they can fully eliminate the tumor.
To overcome this challenge, researchers introduced a gene from a related bacterium that is better able to tolerate oxygen. This change allows the engineered bacteria to survive longer near the tumor’s outer regions.
Engineering Bacteria to Survive
The team also developed a way to activate the oxygen-tolerance gene only when needed, which helps prevent the bacteria from growing in oxygen-rich areas such as the bloodstream. They achieved this using a natural process called quorum sensing.
Quorum sensing involves chemical signals released by bacteria. When enough bacteria accumulate inside a tumor, the signal becomes strong enough to switch on the oxygen-tolerance gene, ensuring it is not activated too early.
In one study, researchers showed that Clostridium sporogenes can be modified to tolerate oxygen. In a follow-up study, they tested the quorum-sensing system by engineering the bacteria to produce a green fluorescent protein.
“Using synthetic biology, we built something like an electrical circuit, but instead of wires we used pieces of DNA,” said Dr. Brian Ingalls, a professor of applied mathematics at Waterloo. “Each piece has its job. When assembled correctly, they form a system that works in a predictable way.”
The team also developed a way to activate the oxygen-tolerance gene only when needed, which helps prevent the bacteria from growing in oxygen-rich areas such as the bloodstream. They achieved this using a natural process called quorum sensing.
Quorum sensing involves chemical signals released by bacteria. When enough bacteria accumulate inside a tumor, the signal becomes strong enough to switch on the oxygen-tolerance gene, ensuring it is not activated too early.
In one study, researchers showed that Clostridium sporogenes can be modified to tolerate oxygen. In a follow-up study, they tested the quorum-sensing system by engineering the bacteria to produce a green fluorescent protein.
“Using synthetic biology, we built something like an electrical circuit, but instead of wires we used pieces of DNA,” said Dr. Brian Ingalls, a professor of applied mathematics at Waterloo. “Each piece has its job. When assembled correctly, they form a system that works in a predictable way.”
Next Steps Toward Clinical Testing
Researchers now plan to combine the oxygen-tolerance gene with the quorum-sensing control system in a single bacterium and test it on tumors in preclinical trials.
The promising project grew out of work by PhD student Bahram Zargar, who was supervised by Ingalls and Dr. Pu Chen, a retired professor of chemical engineering at Waterloo.
Researchers now plan to combine the oxygen-tolerance gene with the quorum-sensing control system in a single bacterium and test it on tumors in preclinical trials.
The promising project grew out of work by PhD student Bahram Zargar, who was supervised by Ingalls and Dr. Pu Chen, a retired professor of chemical engineering at Waterloo.
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