CHICAGO — Researchers at the University of Chicago published a study in Science Advances introducing a new strategy to treat pancreatic cancer. The study reports the use of BifidoSumIL-2, an engineered bacterial strain of Bifidobacterium longum, to deliver immune-stimulating therapy directly inside tumors.

BifidoSumIL-2 treatment suppressed pancreatic tumor growth by selectively activating cancer-fighting T cells in animal models. The therapy is designed to release a modified form of interleukin-2 (IL-2), called SumIL-2, inside tumors. SumIL-2 is an engineered version of IL-2 designed to selectively stimulate cancer-fighting T cells while limiting activation of regulatory T cells.

Bifidobacterium longum is an obligate anaerobe that thrives in low-oxygen environments common in solid tumors but does not grow in oxygen-rich healthy tissues. After systemic injection, the engineered bacteria are cleared from healthy tissues but become active in the low-oxygen regions of tumors. Mark Mimee, PhD, is an Assistant Professor of Microbiology at the University of Chicago.

"Bifidobacterium is an obligate anaerobe, so it doesn't grow in the presence of oxygen," Mimee said. "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."

Ralph Weichselbaum, MD, is the Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago. "A big unmet medical need has been pancreatic cancer, and so that was going to be our mountain to climb," Weichselbaum said. The effects of BifidoSumIL-2 were enhanced when combined with chemotherapy, radiotherapy, or immunotherapy in animal models. "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," Weichselbaum said.

The study is titled Engineered probiotic Bifidobacterium for tumor-targeted pancreatic cancer therapy. The study was supported by funds from the Ludwig Foundation and the National Institutes of Health. BifidoSumIL-2 has not yet been tested in humans. "This was a highly interdisciplinary effort. We had to bring together people who understand bacteria, people who understand tumors, and people who understand the immune system to make something like this possible," Mimee said.

The University of Chicago is a private university in Chicago, Illinois. The University of Chicago received a $1.5 million National Cancer Institute (NCI) R01 award in 2024 to develop microbiome-based cancer therapies, including work on engineered bacteria for tumor targeting. In 2025, the University of Chicago partnered with biotech firm Evelo Biosciences to advance microbiome-based cancer therapies, including preclinical research on probiotic bacteria for immunotherapy delivery.

A 2024 preclinical study published in Science Translational Medicine demonstrated that engineered probiotics could deliver checkpoint blockade nanobodies directly to tumors, achieving significant tumor control in mouse models of pancreatic cancer. In 2023, University of Chicago researchers found that Bifidobacterium species could enhance anti-tumor T cell responses in melanoma models by interacting with dendritic cells in the gut, laying groundwork for later work on BifidoSumIL-2.

The study builds on a precedent established by a 2024 preclinical study in bioRxiv, which showed that engineered Escherichia coli Nissle 1917 could selectively colonize pancreatic tumors and deliver cytotoxic payloads, improving survival in mouse models. This prior work established a framework for tumor-targeting approaches that BifidoSumIL-2 now advances through the use of an obligate anaerobe and engineered cytokine delivery.