A team of researchers at the University of Waterloo has developed a groundbreaking approach to cancer treatment by engineering bacteria known as Clostridium sporogenes. This innovative research, published in the journal ACS Synthetic Biology, aims to use these bacteria to target and consume tumors from the inside out.
Bacteria, often associated with disease, can also serve beneficial roles in the body. The newly engineered C. sporogenes thrive in oxygen-free environments, which is characteristic of solid tumors that contain dead cells. According to Marc Aucoin, a professor of chemical engineering at Waterloo and coauthor of the study, these bacteria enter tumors, utilizing the available nutrients to grow and multiply. “So, we are now colonizing that central space, and the bacterium is essentially ridding the body of the tumor,” Aucoin explained.
This method presents a potential alternative to traditional cancer treatments such as chemotherapy, which can be toxic and limited in efficacy. The unique properties of bacteria not only allow them to target tumors but also help trigger an immune response against cancer. Christopher Johnston, a researcher in genomic medicine at the University of Texas, noted that using microbes could address challenges associated with conventional therapies. “Solid tumors can be notoriously treatment-resistant due to their complex microenvironment,” Johnston stated, emphasizing the promise of harnessing specific bacteria in this context.
Recent studies have shown the potential of engineered bacteria in tumor reduction. For instance, in 2024, research demonstrated that genetically modified E. coli could shrink tumors in mice, while other work involved strains of Salmonella designed to kill cancer cells. While these developments are promising, Aucoin and his team faced significant challenges in their research.
One major obstacle was that the engineered C. sporogenes would perish upon reaching the tumor’s oxygen-rich edges. To combat this, researchers genetically modified the bacteria to tolerate some oxygen levels, allowing them to survive in the vicinity of tumors. This modification was detailed in a 2023 study, which laid the groundwork for their latest findings.
The researchers employed a technique called “quorum sensing” to ensure that the oxygen-resistant gene activated only once the bacteria had sufficiently multiplied within the tumor. This strategic approach optimizes the bacteria’s potential to destroy the tumor. The team also engineered the bacteria to produce a green fluorescent protein, serving as a marker to indicate successful tumor colonization and destruction.
“Using synthetic biology, we built something like an electrical circuit, but instead of wires we used pieces of DNA,” said Brian Ingalls, a professor of applied mathematics at Waterloo and coauthor of the study. Each DNA segment plays a specific role, and their correct assembly creates a predictable system for combating tumors.
Although these findings represent significant progress, the application of this research to human patients remains in the early stages. The Waterloo team now aims to integrate their research on genetic modification and quorum sensing into a single bacterium for use in pre-clinical trials. As the field of bacterial cancer therapies progresses, the potential for these engineered microbes to transform cancer treatment continues to grow.
