Researchers are exploring an unconventional cancer treatment that uses engineered bacteria to target the oxygen-free environments inside tumors.
A University of Waterloo-led team is developing a tool that modifies bacteria to enter solid tumors, grow inside them, and destroy them from within.
The research focuses on Clostridium sporogenes, a soil bacterium that grows only in anaerobic environments, where oxygen is absent. This makes it suitable for targeting the necrotic core of a solid tumor, where dead cancer cells, nutrients, and very low oxygen levels create conditions the bacterium can survive in.
According to Dr. Marc Aucoin, a chemical engineering professor at Waterloo, bacterial spores enter the tumor and grow in its oxygen-free, nutrient-rich center.
“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,” Aucoin said. “So, we are now colonizing that central space, and the bacterium is essentially ridding the body of the tumor.”
The main challenge is that Clostridium sporogenes struggles to survive near the tumor’s outer edges, where small amounts of oxygen are present. This prevents the bacteria from fully destroying the tumor.
To address this, researchers added a gene from a related bacterium with better oxygen tolerance. The modification allows Clostridium sporogenes to survive longer near the outer tumor region, where oxygen levels are low but not completely absent.
The team also needed to control when the oxygen-tolerance gene turns on. If activated too early, the bacteria could survive in oxygen-rich parts of the body, such as the bloodstream, which would be unsafe.
To solve this, researchers used quorum sensing, a natural bacterial communication system. Bacteria release chemical signals, and once the bacterial population inside the tumor becomes large enough, the signal can activate the oxygen-tolerance gene.
In simple terms, the gene is designed to switch on only after enough bacteria have gathered inside the tumor. This helps keep the bacteria focused on the tumor environment and prevents early activation elsewhere in the body.
In one study, the researchers showed that Clostridium sporogenes can be engineered to tolerate oxygen. In a follow-up study, they tested the quorum sensing system by making the bacteria produce a green fluorescent protein, confirming that the genetic switch was working.
The next step is to combine the oxygen-tolerance gene and quorum-sensing control system in a single bacterium and test it on a tumor in pre-clinical trials.