Researchers at the University of Waterloo have made significant progress in cancer treatment by engineering bacteria known as Clostridium sporogenes to target and consume tumors from the inside. This innovative approach utilizes the unique properties of these bacteria, which thrive in oxygen-free environments, making solid tumors an ideal breeding ground. The findings were published in the journal ACS Synthetic Biology.
Solid tumors often consist of dead cells and a lack of oxygen, creating a nutrient-rich environment that is perfect for the growth of these modified bacteria. According to Marc Aucoin, a chemical engineering professor at Waterloo and co-author of the study, “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.”
This research offers a potential alternative to conventional cancer treatments, including chemotherapy, radiation therapy, and immunotherapy, which can be toxic and have limited effectiveness. The engineered bacteria may also stimulate an immune response against cancer cells, presenting a dual action in fighting the disease.
Christopher Johnston, a genomic medicine researcher at the University of Texas who has researched bacteria’s potential to invade human tumors, stated, “Using ‘bugs as drugs’ offers a promising solution to overcome some of the challenges with traditional cancer therapies.” He noted that solid tumors, which account for the majority of adult cancers, are often resistant to treatments due to their complex microenvironment.
In addition to the current study, previous research published in 2024 demonstrated that engineered E. coli could shrink tumors in animal models. Other studies have focused on genetically modified strains of Salmonella that selectively kill cancer cells.
Despite the promising advances, the research team faced challenges. One significant hurdle was the exposure of the bacteria to oxygen when they reached the edges of tumors, which could prove fatal. To address this issue, the researchers genetically modified the bacteria to enhance their oxygen tolerance. This adaptation was reported in a 2023 study.
The researchers employed a technique known as “quorum sensing” to ensure that the oxygen-resistant gene activated only after the bacteria had multiplied sufficiently within the tumor. This strategic modification allows the bacteria to withstand the oxygen-rich environment at the tumor’s periphery while effectively targeting and destroying the tumor core.
To visually signal their success, the team engineered the bacteria to produce a green fluorescent protein, indicating when they have effectively colonized the tumor. As Brian Ingalls, a professor of applied mathematics at Waterloo and co-author, explained, “Using synthetic biology, we built something like an electrical circuit, but instead of wires we used pieces of DNA.”
While these studies provide a promising foundation, thorough testing of the bacteria’s effectiveness in human cancer treatment is still in the early stages. The Waterloo research team is now working to combine their findings on oxygen resistance and quorum sensing into a single bacterium for pre-clinical trials.
As this research progresses, it may pave the way for innovative and less toxic approaches to cancer treatment, opening new avenues in the ongoing battle against this disease.
