Scientists at the University of Chicago have engineered a common probiotic bacterium to deliver cancer-fighting therapy directly into pancreatic tumors, offering a novel approach to treating one of the most difficult cancers to fight. In animal models, the engineered bacteria activated immune cells and slowed tumor growth, with even stronger results when combined with chemotherapy, radiation, or immunotherapy.

Why Is Pancreatic Cancer So Hard to Treat?

Pancreatic tumors are notoriously resistant to immune system attacks. They create what researchers call a "cold" tumor microenvironment, which prevents immune cells from mounting an effective response. This resistance has limited the benefits of immunotherapies that have successfully transformed treatment for other cancers. The University of Chicago team set out to overcome this barrier by delivering immune stimulation directly to the tumor site.

How Does the Engineered Bacteria Therapy Work?

The researchers engineered Bifidobacterium longum, a probiotic bacterium commonly found in yogurt and other fermented foods, to carry a treatment called BifidoSumIL-2 into pancreatic tumors. This therapy delivers a modified version of interleukin-2 (IL-2), an immune signaling molecule that activates cancer-fighting T cells. The key innovation is using an engineered form called SumIL-2, which is designed to favor cancer-fighting T cells while limiting activation of regulatory T cells that can suppress antitumor activity.

Bifidobacterium proved to be an ideal delivery vehicle because it grows in low-oxygen environments. Many solid tumors, including pancreatic cancers, contain regions with minimal oxygen, while healthy tissues generally have sufficient oxygen to restrict the bacterium's growth. This selective targeting helps concentrate the immune-stimulating molecule within the cancer rather than throughout the body.

"Bifidobacterium is not the easiest organism to work with. It's anaerobic, it grows slowly, and the genetic tools for manipulating it are much more limited compared to model bacteria like E. coli. A lot of the work was just figuring out how to reliably engineer it," explained Mark Mimee, Assistant Professor of Microbiology at the University of Chicago.

Mark Mimee, Assistant Professor of Microbiology at the University of Chicago

What Did the Animal Studies Show?

In animal experiments, BifidoSumIL-2 accumulated selectively inside tumors, stimulated immune activity, and slowed pancreatic cancer growth. The therapy altered the tumor microenvironment by increasing the activity of CD8+ T cells, which are immune cells capable of recognizing and destroying cancer cells. When researchers combined the bacterial treatment with established therapies, the results were even more promising.

• Chemotherapy: The combination produced stronger tumor control and improved survival compared to chemotherapy alone
• Radiation Therapy: Pairing BifidoSumIL-2 with radiation enhanced both tumor control and survival outcomes
• Immunotherapy: Anti-PD-L1 immunotherapy showed improved results when combined with the bacterial treatment

"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," stated Ralph Weichselbaum, Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago.

Ralph Weichselbaum, Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago

What Happens Next?

BifidoSumIL-2 has not yet been tested in humans. Before clinical trials can begin, researchers must examine several critical questions. Future work will need to evaluate long-term safety, determine whether the therapy produces effects outside the tumor, assess how long the immune response persists, and explore whether the bacteria can be taken orally instead of injected. Researchers also plan to test the approach alongside newer pancreatic cancer treatments, including KRAS inhibitors.

This work is part of a broader "bugs as drugs" strategy that uses engineered probiotic bacteria to carry therapies into difficult-to-treat tumors. By producing immune treatments directly at the cancer site, these bacteria could potentially strengthen local effects while reducing exposure in healthy parts of the body. The research was published in Science Advances on July 23, 2026, and was supported by funds from the Ludwig Foundation and the National Institutes of Health.

"A big unmet medical need has been pancreatic cancer, and so that was going to be our mountain to climb," noted Ralph Weichselbaum.

Ralph Weichselbaum, Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago