Combining discoveries in cancer immunology with sophisticated genetic engineering, Columbia University researchers have created a sort of “bacterial suicide squad” that targets tumors, attracting the host’s own immune cells to the cancer to destroy it. The new work, published today in Science Advances, marks a major step forward in efforts to enlist non-pathogenic bacteria to combat cancer.
Scientists have known for years that some species of bacteria can thrive inside tumors. “It’s been speculated that this is due to the low pH, necrotic and immune-excluded environment … that’s unique to the core of a tumor and supports bacterial growth while preventing clearance of bacteria by immune cells,” says Nicholas Arpaia, PhD, assistant professor of microbiology and immunology at Columbia’s Vagelos College of Physicians and Surgeons and senior author on the new paper. In an ongoing collaboration with Tal Danino, PhD, associate professor of biomedical engineering at Columbia Engineering, Dr. Arpaia has been building an anti-tumor strategy around that phenomenon.
At the core of the approach is a probiotic strain of the bacterium E. coli, engineered with a synchronized lysis circuit. Once the bacterial cells reach a quorum inside a tumor, the circuit triggers, causing most of the bacteria to lyse, or break apart, releasing their contents. Previously, the investigators have added genes to the microbes encoding proteins that block tumor cell growth, or that flag the tumor for digestion by immune cells. “My graduate student, Thomas [Savage], had the idea of potentially utilizing this platform to deliver chemokines,” says Dr. Arpaia, who is also a member of the Herbert Irving Comprehensive Cancer Center (HICCC) at NewYork-Presbyterian/Columbia University Irving Medical Center.
Attracting killer T cells
Immunologists have found that different chemokines, immune system signaling proteins, attract different types of immune cells and stimulate them to respond in specific ways. In the new work, the team included a mutated version of a human chemokine gene that attracts “killer” T cells. “Although T cell responses that are specific to tumor-derived antigens are primed, sometimes what will happen is that despite there being primed anti-tumor T cells, they fail to be recruited into the tumor environment,” says Dr. Arpaia.
