Tumor-targeting Salmonella engineered to boost colon cancer survival

Scientists have engineered Salmonella bacteria to self-destruct inside tumors, releasing signals that spark powerful immune hubs and shrink colon cancer in mice, opening the door to “living medicines” against deadly cancers.

In a new study by the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine) and Central South University, China, researchers have explored a promising avenue in colorectal cancer treatment, boosting special immune cell clusters called mature tertiary lymphoid structures (mTLSs), that form near tumors and are linked to better survival.

“This work provides compelling evidence that mTLSs can be therapeutically induced using synthetic biotics,” said co-corresponding author Xiaoyuan (Shawn) Chen, PhD, Professor in Medicine and Technology and Director of the Nanomedicine Translational Research Program (TRP) at NUS Medicine. “Our engineered strain stimulates a key immune signaling pathway, LIGHT-HVEM, to activate group 3 innate lymphoid cells and kickstart T cell-mediated antitumor responses.”

The researchers started with a weakened strain of Salmonella typhimurium, which has already been shown to be safe in earlier human trials for other cancers. This strain naturally homes in on tumors.

They engineered the bacteria by adding a synchronized lysis circuit (SLC), so they would self-destruct in unison once they reached high density inside tumors. Upon this lysis, the bacteria release a protein called LIGHT, which binds to a receptor called HVEM on immune cells, thereby driving strong immune activation.

Image source: Wikimedia Commons/NIAID, CC BY 4.0.