Although cancer immunotherapy has revolutionized the treatment of many cancers, treating pancreatic cancer remains particularly challenging. One of the main reasons is that pancreatic tumors often create a “cold” tumor microenvironment, where the tumor prevents immune cells from mounting a strong attack.
In a new study published in scientific progressresearchers at the University of Chicago report a promising new strategy to overcome this barrier using BifidoSumIL-2, a genetically engineered bacterial strain. Bifidobacterium longuma probiotic bacteria naturally present in the intestine, that provides immune stimulation therapy directly inside the tumor.
This treatment inhibited pancreatic tumor growth by selectively activating cancer-fighting T cells. The effect was even greater when combined with chemotherapy, radiation therapy, and immunotherapy. This study highlights BifidoSumIL-2 as a potentially powerful approach to improve treatment response in pancreatic cancer.
New bacterial delivery strategies
A major unmet medical need is pancreatic cancer, and that will be the mountain we need to climb. ”
Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor and Professor of Radiation and Cellular Oncology, University of Chicago
The new treatment, 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 that help the body fight cancer. However, conventional IL-2 therapy can cause harmful side effects and may also activate immune cells that suppress anti-tumor responses.
To address this, the research team used SumIL-2, a modified version of IL-2 designed to more selectively stimulate cancer-fighting T cells while limiting the activation of regulatory T cells. By putting SumIL-2 inside Bifidobacterium longumThe researchers aimed to focus the treatment directly within the tumor.
This research required expertise across multiple disciplines, from microbiology and synthetic biology to oncology and immunology.
“This was a very interdisciplinary effort,” said Dr. Mark Maimie, assistant professor of microbiology at the University of Chicago. “To make something like this possible, we needed to bring together people who understood bacteria, people who understood tumors, and people who understood the immune system.”
manipulate bacteria
Bifidobacterium were an attractive delivery vehicle because they grow in an anaerobic, or hypoxic, environment, a common feature of many solid tumors, including pancreatic tumors. Healthy tissues generally have high oxygen levels, which are less favorable for bacterial growth.
”Bifidobacterium “It’s an obligate anaerobe, so it doesn’t grow in the presence of oxygen,” Maimy said. After systemic injection, bacteria are cleared from oxygen-rich healthy tissues, but can become active in hypoxic areas of tumors.
This tumor-seeking behavior allows bacteria to behave like microscopic drug factories. Essentially, these tiny factories produce SumIL-2 only at tumor sites where the drug is needed. The researchers pointed out that: Bifidobacterium It has a good safety profile in preclinical models and is already widely recognized as a probiotic microorganism. It is commonly found in yogurt and is therefore generally recognized as a safe, ready-made probiotic.
”Bifidobacterium “It’s not the easiest creature to work with,” Maimie said. “It’s anaerobic, slow growing, and the genetic tools to manipulate it are much more limited compared to model bacteria such as: Escherichia coli. A lot of the work was just figuring out how to design it reliably. ”
Increase effectiveness with combination therapy
In animal models, BifidoSumIL-2 selectively accumulated in tumors, activated immune responses, and slowed pancreatic tumor growth. The therapy also helped reshape the tumor microenvironment by increasing the activity of cancer-fighting CD8+ T cells.
This treatment becomes even more effective when combined with standard cancer treatments. Combining BifidoSumIL-2 with chemotherapy, radiotherapy, or anti-PD-L1 immunotherapy further improved tumor control and survival compared to monotherapy.
“This combination potential is one of the most important findings of this study. BifidoSumIL-2 not only works alone, but also in combination with radiation therapy, chemotherapy, and immunotherapy,” Weichselbaum said.
Although the results are promising, BifidoSumIL-2 has not yet been tested in humans. Future studies will need to assess long-term safety, potential off-target effects, durability of immune responses, and whether bacteria can be delivered orally rather than by injection. The researchers are also interested in combining this approach with new pancreatic cancer treatments such as KRAS inhibitors.
The study highlights the growth of the “bug-as-medicine” strategy, in which genetically engineered probiotic bacteria may offer a new way to deliver immunotherapy directly to hard-to-treat tumors while reducing side effects elsewhere in the body.
the study, “Genetically engineered probiotic bifidobacteria for tumor-targeted pancreatic cancer treatment“Supported by funds from the Ludwig Foundation and the National Institutes of Health.”.
Other authors include Jaehyun Lee, Kaiting Yang, Christina Nowicki, Wei Liu, Emile Naccasha and Hua Liang from the University of Chicago. Zhichen Sun of the University of Texas Southwestern at Dallas; Yang-Xin Fu, Tsinghua University, Beijing, China;
sauce:
University of Chicago Medical Center
Reference magazines:
Lee, J. Others. (2026). artificial probiotics Bifidobacterium For tumor-targeted pancreatic cancer treatment. scientific progress. DOI: 10.1126/sciadv.adz1388. https://www.science.org/doi/10.1126/sciadv.adz1388
