Scientists at the University of Chicago have engineered a common gut probiotic to invade pancreatic tumors and turn them into targets for the immune system, an approach that slowed tumor growth in mice and showed even stronger effects when paired with standard cancer treatments. The findings, published this month in Science Advances, offer a new strategy against one of the hardest cancers to treat.
The engineered strain, called BifidoSumIL-2, is built from Bifidobacterium longum, a bacterium already found in yogurt and dietary supplements. Researchers modified it to manufacture a tumor-tuned version of interleukin-2, an immune signaling protein that switches on cancer-killing T cells while limiting activation of the regulatory T cells that normally shield tumors from attack. Because Bifidobacterium thrives only in low-oxygen conditions, it naturally colonizes the oxygen-starved core of solid tumors and is cleared from healthy, oxygen-rich tissue — letting the bacteria concentrate the therapy exactly where it is needed rather than flooding the whole body.
Stronger together
In the animal studies described in the University of Chicago Medicine announcement, BifidoSumIL-2 slowed pancreatic tumor growth on its own, and its effect grew substantially when combined with chemotherapy, radiation therapy, or anti-PD-L1 immunotherapy. That combinability matters because pancreatic cancer is notoriously resistant to immunotherapy alone — its tumors are typically walled off by dense tissue and starved of the immune cells that other cancers rely on for a response.
Pancreatic cancer remains one of the deadliest common malignancies, with a five-year survival rate still under 15% in the United States, largely because it is usually caught late and responds poorly to existing drugs. Researchers have spent the past decade exploring engineered microbes as living drug factories, since bacteria can be programmed to sense a tumor's environment and release payloads only there — reducing the toxic side effects that come from therapies that circulate freely through the bloodstream.
"A big unmet medical need has been pancreatic cancer, and so that was going to be our mountain to climb," said Dr. Ralph Weichselbaum, chair of radiation and cellular oncology at the University of Chicago and a senior author of the study.
This combination potential is one of the study's most important findings; BifidoSumIL-2 not only works by itself — it works with radiotherapy, chemotherapy, and immunotherapy.
Dr. Ralph Weichselbaum, University of Chicago Medicine
Co-author Mark Mimee, an assistant professor of microbiology who helped engineer the strain, described the project as spanning several disciplines not usually in the same room. "This was a highly interdisciplinary effort," he said, noting that Bifidobacterium is slow-growing, oxygen-intolerant, and harder to genetically manipulate than lab workhorses like E. coli. The work, funded by the Ludwig Foundation and the National Institutes of Health, is still confined to animal models; the team's next step is preparing the engineered strain for human safety trials, with researchers cautioning that years of additional testing lie ahead before it could reach patients.
