University of Chicago Researchers Develop Engineered Probiotic to Target Pancreatic Cancer

Researchers at the University of Chicago have introduced a novel treatment strategy for pancreatic cancer, a disease that has proven particularly resistant to existing immunotherapy advancements. Their study, published in Science Advances, focuses on using BifidoSumIL-2, an engineered strain of the probiotic bacterium Bifidobacterium longum, to deliver immune-stimulating therapies directly into tumors, potentially enhancing the efficacy of cancer treatments.

Current pancreatic cancer treatments face significant challenges due to the tumor’s “cold” microenvironment, which inhibits immune cell activity. Ralph Weichselbaum, MD, the Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago, emphasized the urgent need for innovative approaches in tackling pancreatic cancer, citing it as a substantial medical challenge.

BifidoSumIL-2 is designed to release a modified form of interleukin-2 (IL-2) specifically within tumor sites. IL-2 is known for its ability to activate T cells that fight cancer, but traditional IL-2 therapy carries a risk of serious side effects and can inadvertently weaken the immune response by also activating regulatory T cells.

To mitigate these issues, the research team utilized a modified version of IL-2, termed SumIL-2, which selectively stimulates cancer-fighting T cells while minimizing activation of regulatory cells. The strategy employs Bifidobacterium longum as a delivery mechanism, ensuring that the therapeutic compound is concentrated within tumors rather than being distributed throughout the body.

The development of this treatment was an interdisciplinary effort involving specialists in microbiology, synthetic biology, oncology, and immunology. Mark Mimee, PhD, an Assistant Professor of Microbiology at UChicago, highlighted the collaborative nature of the project, stating, “We had to bring together people who understand bacteria, people who understand tumors, and people who understand the immune system.”

The anaerobic growth characteristics of Bifidobacterium provide a distinct advantage for tumor targeting. This bacterium thrives in low-oxygen environments typical of many solid tumors, including pancreatic cancers, but not in healthier tissues where oxygen levels are higher. As a result, the engineered bacteria can act as localized drug factories, producing SumIL-2 where it is most needed.

Preclinical tests demonstrated that BifidoSumIL-2 effectively localized within pancreatic tumors, stimulated immune activity, and slowed tumor growth. Moreover, when used in combination with established cancer treatments such as chemotherapy, radiation therapy, or anti-PD-L1 immunotherapy, the therapy showed enhanced effectiveness, leading to improved tumor control and extended survival compared to single treatments.

Despite these promising results, BifidoSumIL-2 has yet to enter human clinical trials. Future studies will evaluate its long-term safety, potential off-target effects, immune response duration, and the possibility of oral administration. Researchers also plan to explore its effectiveness alongside new pancreatic cancer therapies, including KRAS inhibitors.

This research contributes to a growing interest in the “bugs as drugs” approach, where engineered probiotic bacteria are harnessed to deliver targeted therapies directly to tumors, focusing treatment where it is most needed while minimizing side effects elsewhere in the body.

The study was supported by the Ludwig Foundation and the National Institutes of Health. Additional contributors include Jaehyun Lee, Kaiting Yang, Christina Nowicki, Wei Liu, Emile Naccasha, and Hua Liang from the University of Chicago, as well as Zhichen Sun from the University of Texas Southwestern, Dallas, and Yang-Xin Fu from Tsinghua University, Beijing, China.

UChicago Medicine continues to lead in cancer care and research, with plans to open the AbbVie Foundation Cancer Pavilion in April 2027, Chicago’s first freestanding cancer pavilion, designed to offer advanced diagnostics and innovative treatment options.