Engineered probiotic bacteria boost immune attack against pancreatic cancer

Cancer immunotherapies have transformed treatment for many cancers, but pancreatic cancer remains especially difficult to treat. One major reason is that pancreatic tumors often create a "cold" tumor microenvironment, where the tumor prevents immune cells from mounting a strong attack.

The treatment suppressed pancreatic tumor growth by selectively activating cancer-fighting T cells. The effects were further enhanced when combined with chemotherapy, radiotherapy or immunotherapy. The study highlights BifidoSumIL-2 as a potentially powerful approach for improving treatment response in pancreatic cancer.

A novel bacterial delivery strategy

The new therapy, called BifidoSumIL-2, is designed to release a modified form of interleukin-2 (IL-2) inside tumors. IL-2 is a powerful immune molecule that activates T cells, which help the body fight cancer. However, traditional IL-2 therapy can cause harmful side effects and may also activate immune cells that suppress the antitumor response.

The work required expertise across multiple fields, from microbiology and synthetic biology to oncology and immunology.

Engineering the bacteria

Enhanced effects with combination therapy

In animal models, BifidoSumIL-2 selectively accumulated in tumors, activated immune responses, and slowed pancreatic tumor growth. The treatment also helped reshape the tumor microenvironment by increasing the activity of cancer-fighting CD8+ T cells.

The therapy became even more effective when combined with standard cancer treatments. Pairing BifidoSumIL-2 with chemotherapy, radiation therapy, or anti-PD-L1 immunotherapy further improved tumor control and survival compared with single treatments alone.

"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.

Although the results are promising, BifidoSumIL-2 has not yet been tested in people. Future studies will need to evaluate long-term safety, possible off-target effects, durability of the immune response, and whether the bacteria can be delivered orally rather than by injection. Researchers are also interested in combining this approach with newer pancreatic cancer therapies, including KRAS inhibitors.

The study highlights a growing "bugs as drugs" strategy, in which engineered probiotic bacteria could provide a new way to deliver immune therapies directly into hard-to-treat tumors while limiting side effects elsewhere in the body.

The study, "Engineered probiotic Bifidobacterium for tumor-targeted pancreatic cancer therapy" was supported by funds from the Ludwig Foundation and the National Institutes of Health.

Additional authors include Jaehyun Lee, Kaiting Yang, Christina Nowicki, Wei Liu, , Emile Naccasha, and Hua Liang from the University of Chicago; Zhichen Sun from the University of Texas Southwestern, Dallas; and Yang-Xin Fu from the Tsinghua University, Beijing, China.

Source:

University of Chicago Medical Center

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