Researchers at the University of Waterloo are developing a novel cancer treatment that uses specially engineered bacteria to destroy tumors from the inside. The approach exploits microbes that naturally thrive in oxygen-free environments, making the inner regions of solid tumors an ideal target.
By using bacteria that grow where oxygen is absent, scientists aim to create a treatment capable of reaching parts of tumors that conventional therapies often struggle to access.
How Bacteria Target Tumor Environments
According to Marc Aucoin, a chemical engineering professor at the University of Waterloo, bacterial spores can enter tumors and find an environment rich in nutrients but lacking oxygen.
“Bacteria spores enter the tumor and encounter a space with abundant nutrients and no oxygen, which this organism prefers. As a result, it begins consuming those nutrients and expanding in size. Eventually, the bacterium colonizes the central space and gradually eliminates the tumor,” he explained.
At the centre of this strategy is Clostridium sporogenes, a bacterium commonly found in soil. Because this microbe can survive only in environments completely devoid of oxygen, the inner core of many solid tumors—often filled with dead cells and lacking oxygen—creates ideal conditions for it to multiply and spread.
Overcoming the Oxygen Challenge
However, the researchers faced an important obstacle. As the bacteria expand outward and reach tumor regions exposed to small amounts of oxygen, they begin to die before completely destroying the cancer.
To address this limitation, the team inserted a gene from a related bacterium that tolerates oxygen more effectively. This genetic modification allows the engineered microbes to survive longer when they encounter oxygen near the tumor’s outer regions.
Using Quorum Sensing for Safety and Control
Nevertheless, the researchers also needed to control when the oxygen-tolerance feature becomes active. If the gene switched on too early, the bacteria could survive in oxygen-rich environments such as the bloodstream, creating potential safety risks.
To solve this problem, the scientists used a natural bacterial communication mechanism known as Quorum Sensing.
Quorum sensing works through chemical signals released by bacteria. As the number of bacteria increases, these signals accumulate and become stronger. Only when enough bacteria gather inside the tumor does the signal reach the threshold required to activate the oxygen-resistant gene. Consequently, the bacteria turn on their survival mechanism only at the appropriate stage of tumor colonization.
Synthetic Biology Enables DNA-Based Circuits
In an earlier study, researchers demonstrated that Clostridium sporogenes could be genetically modified to better tolerate oxygen. Subsequently, the team tested their quorum-sensing system by programming the bacteria to produce a green fluorescent protein. This allowed them to confirm that the genetic switch activated precisely when intended.
Brian Ingalls, a professor of applied mathematics at the University of Waterloo, explained the concept behind the design.
“Using synthetic biology, we created something similar to an electrical circuit. However, instead of wires, we used pieces of DNA. Each component performs a specific function, and when assembled correctly, they create a system that behaves predictably,” he said.
Next Steps Toward Pre-Clinical Testing
The next phase of the research involves combining the oxygen-tolerance gene and the quorum-sensing control system within a single engineered bacterium. Researchers will then evaluate the system in pre-clinical models to determine its effectiveness against tumors.
If successful, this strategy could open new possibilities for treating cancers that are difficult to reach with traditional therapies.
Collaborative Research Driving Innovation
As reported by Science Daily, the project began with research led by PhD student Bahram Zargar under the supervision of Brian Ingalls and Pu Chen, a retired professor of chemical engineering at the University of Waterloo.
The initiative highlights the university’s emphasis on interdisciplinary innovation, bringing together experts from engineering, mathematics, and life sciences to translate scientific discoveries into practical medical solutions.
Furthermore, the research team has partnered with the Center for Research on Environmental Microbiology (CREM Co Labs), a Toronto-based company co-founded by Bahram Zargar. The collaboration also involves Sara Sadr, a former Waterloo doctoral student who played a key role in advancing the research.