Engineered Gut Bacteria Slow Pancreatic Tumor Growth in Animal Study

Researchers at the University of Chicago have engineered a strain of probiotic bacteria to carry cancer-fighting treatment directly into pancreatic tumors, an approach that slowed tumor growth in animal models, according to a study published in Science Advances. Pancreatic cancer has long resisted immunotherapy because tumors create a "cold" environment that blocks immune cells from attacking effectively.

The team used BifidoSumIL-2, an engineered strain of Bifidobacterium longum, a probiotic bacterium naturally found in the gut, to release a modified version of interleukin-2 (IL-2), an immune-signaling molecule that activates cancer-fighting T cells, once it reaches a tumor. Conventional IL-2 treatment can cause serious side effects and also stimulate immune cells that weaken the antitumor response, so the researchers engineered a modified form, called SumIL-2, designed to more precisely activate cancer-fighting T cells.

Bifidobacterium longum grows only in low-oxygen environments, a condition common inside solid tumors such as pancreatic cancer but not in healthy, oxygen-rich tissue. "Bifidobacterium is an obligate anaerobe, so it doesn't grow in the presence of oxygen," said Mark Mimee, Assistant Professor of Microbiology at the University of Chicago, meaning the bacteria are cleared from healthy tissue but become active inside tumors, functioning as microscopic drug factories.

In animal models, BifidoSumIL-2 gathered inside tumors, increased the activity of cancer-fighting CD8+ T cells, and slowed pancreatic tumor growth. Results improved further when it was combined with chemotherapy, radiation therapy or anti-PD-L1 immunotherapy. "This combination potential is one of the study's most important findings," said Ralph Weichselbaum, chair of Radiation and Cellular Oncology at the university. The treatment has not yet been tested in humans, and researchers still need to study its long-term safety and whether it could eventually be given orally.