Engineered Gut Bacteria Boost Survival Rates in Colorectal Cancer Treatment

Recent advances in synthetic biology and immunotherapy have led scientists from the Yong Loo Lin School of Medicine at the National University of Singapore and Central South University in China to develop an innovative bacterial therapy targeting colorectal cancer (CRC). The researchers engineered a strain of gut-homing bacteria capable of stimulating the immune system to mount a robust attack against tumor cells.

The core of this approach involves genetically modifying a strain of Salmonella typhimurium to colonize tumor tissue specifically. Once localized within the tumor environment, this engineered bacteria releases a therapeutic protein called LIGHT, which promotes the formation of mature tertiary lymphoid structures (mTLSs). These immune 'hubs' serve as sites where immune cells can congregate and activate, significantly enhancing the body's antitumor response.

Antitumor immune responses are crucial for fighting cancer, as they involve immune cells recognizing and destroying cancer cells. Tumors, however, often develop mechanisms to evade or suppress immune detection, creating a microenvironment that hinders effective immune attack. Strengthening the body's immune response against tumors has shown promise in improving treatment outcomes and extending survival.

Colorectal cancer remains a major global health challenge, being the second leading cause of cancer-related deaths worldwide, accounting for over 9% of all cancer fatalities. Current treatment options are often limited, especially at advanced stages, highlighting the need for new therapies.

This study, published in Science Translational Medicine, demonstrates that the engineered bacteria successfully colonized tumors in laboratory models, induced the formation of immune-boosting structures, suppressed tumor growth, and improved survival rates. Additionally, the therapy was well tolerated, showing high biocompatibility and no off-target effects in other organs. It also helped restore healthy gut microbiota, which plays a vital role in overall health.

Professor Shawn Chen Xiaoyuan from NUS highlighted that this approach activates a key immune pathway (LIGHT-HVEM) to stimulate immune cells like group 3 innate lymphoid cells and T cells, which are essential in attacking tumors. Co-lead author Professor Pengfei Rong emphasized that this strategy could lead to the development of programmable 'living medicines' that fundamentally change how the tumor microenvironment is managed.

Next steps involve rigorous testing and clinical trials to evaluate safety and effectiveness in human patients. This revolutionary approach could pave the way for novel treatments that harness and enhance the body's own immune defenses against colorectal and potentially other cancers.