Scientists Transform Gut Bacteria Into Weapons Against Pancreatic Cancer

What if "good" gut bacteria could be transformed into weapons against one of the world's deadliest cancers? Scientists have genetically modified probiotics to deliver a powerful treatment directly to the tumor, strengthening the immune system and reducing cancer growth in laboratory tests. The discovery could usher in a new era in the fight against difficult-to-treat tumors.

Pancreatic cancer is among the most aggressive and difficult types to treat. In many cases, it is only discovered when it is already advanced, and even with surgery, chemotherapy, or radiotherapy, the chances of success are still limited.

One of the biggest challenges is that this tumor creates a kind of "shield" around itself, preventing the immune system from recognizing and attacking the cancerous cells. Therefore, scientists worldwide are searching for new ways to break through this barrier and transform the body itself into an ally against the disease.

It was precisely this challenge that motivated a team of researchers to develop a highly innovative strategy: genetically modifying probiotic bacteria, those considered beneficial to the gut, so that they act as small drug factories directly inside the tumor.

The idea is simple, but extremely ingenious. Instead of administering a drug that circulates throughout the body and can cause significant side effects, these bacteria travel to the tumor and release the therapeutic substance exactly where it is needed.

To test this approach, researchers used a bacterium called Bifidobacterium longum, a microorganism naturally found in the human gut and widely known for its use as a probiotic. It was modified in the laboratory to continuously produce a special version of an immune system protein called interleukin 2.

This modified version was designed to primarily stimulate immune cells responsible for attacking tumors, avoiding the activation of another group of cells that normally reduces the immune response. These bacteria were then administered to mice with pancreatic cancer and monitored throughout the treatment.

An interesting detail is that these bacteria possess a very useful characteristic: they prefer to live in low-oxygen environments, exactly as happens inside many tumors. This causes them to accumulate naturally in the cancer region, functioning as a highly targeted delivery system.

Bifidobacterium longum

During the experiments, scientists monitored tumor growth, analyzed which immune system cells were present in the region, and also assessed whether combining the new therapy with traditional treatments, such as chemotherapy, radiotherapy, and immunotherapy, could further enhance the results.

The results were quite encouraging. The modified bacteria managed to reach the tumors and remain there, continuously releasing the therapeutic protein. This significantly increased the presence of immune cells capable of destroying cancer and reduced the influence of cells that normally block the immune response. 

As a result, tumor growth decreased significantly. When this strategy was combined with chemotherapy, radiotherapy, or immunotherapy, the effects were even greater, showing that different treatments can act in a complementary way.

Although the study has only been conducted on laboratory animals, it represents an important advance in the search for smarter cancer treatments. Instead of indiscriminately attacking the entire organism, the idea is to use beneficial bacteria as vehicles to transport drugs directly to the tumor, making the treatment potentially more effective and with fewer side effects.

If future research confirms these results in humans, this strategy could pave the way for a new generation of therapies against pancreatic cancer and other tumors that currently respond very poorly to available treatments.

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Engineered probiotic Bifidobacterium for tumor-targeted pancreatic cancer therapy

Jaehyun Lee, Kaiting Yang, Christina A. Nowicki, Wei Liu, Kangdi Li, Emile Naccasha, Zhichen Sun, Yang-Xin Fu, Hua Liang, Ralph R. Weichselbaum, and Mark Mimee

Science Advances. 23 July 2026, vol. 12, n. 30

DOI: 10.1126/sciadv.adz1388

Abstract: 

Pancreatic ductal adenocarcinoma (PDAC) presents a substantial challenge due to its resistance to cancer treatments. This limited efficacy is, in part, attributed to the immunosuppressive tumor microenvironment (TME), which impairs effector T (Teff) cell activity. Interleukin-2 (IL-2) is a key cytokine for T cell activation, but its therapeutic use is limited by a short half-life, systemic toxicity, and regulatory T (Treg) activation. To address this limitation, we engineered Bifidobacterium longum, a probiotic obligate anaerobe that selectively colonizes the TME, to continuously secrete Super-mutant IL-2 (SumIL-2), an engineered IL-2 variant that preferentially activates Teff cells over Treg cells, thereby delivering SumIL-2 selectively to the tumor (BifidoSumIL-2). Systemic administration of BifidoSumIL-2 significantly suppressed tumor growth in both subcutaneous tumors and orthotopic PDAC in mice, inducing an improved Teff/Treg ratio. Combining BifidoSumIL-2 with chemotherapy, radiation, and immunotherapy further restrained orthotopic PDAC growth, highlighting its therapeutic potential for difficult-to-treat cancers like PDAC.