Researchers from the University of Chicago have developed an innovative strategy for treating pancreatic cancer, one of the most resistant cancers to traditional immunotherapy.
The strategy relies on a genetically modified probiotic bacterium, called BifidoSumIL-2, that can deliver an immune-boosting drug directly into tumors.
The problem with pancreatic cancer lies in its ability to create a microclimate around the tumor, preventing immune cells from effectively attacking it. However, in animal models, the new treatment has been able to inhibit tumor growth by selectively activating cancer-fighting T cells, thereby reshaping the tumor's environment and making it more responsive to treatment.
The treatment relies on Bifidobacterium longum, a probiotic bacterium naturally found in the gut and used in yogurt production, which has been genetically engineered to act as a "microscopic drug factory." This bacterium has a unique ability to thrive in low-oxygen environments, a common characteristic of solid tumors such as pancreatic cancer, while being expelled from healthy, oxygen-rich tissues, making it a precise and safe delivery vehicle.
The new treatment carries a powerful immune molecule called interleukin-2 (IL-2), but in a modified form known as SumIL-2. It is designed to activate cancer-fighting T cells while reducing the activation of other immune cells that may suppress the immune response, thus limiting the side effects that were a hurdle in previous immunotherapies.
The results, published in the journal Science Advances, showed that the treatment was not only effective on its own, but also became more potent when combined with conventional therapies. Combining BifidoSumIL-2 with chemotherapy, radiotherapy, or immunotherapy (anti-PD-L1) improved tumor control and increased survival rates compared to using any of these treatments alone.
Dr. Ralph Feichselbaum, chief of the Department of Radiation Therapy and Cellular Oncology at the University of Chicago, said: "Pancreatic cancer has always been a major medical challenge for which we have not found an effective solution. What is encouraging about these results is that the treatment does not work alone, but rather is integrated with radiation, chemotherapy and immunotherapy, which significantly enhances its effectiveness."
For his part, Dr. Mark Mimi, Assistant Professor of Microbiology at the university, explained that this achievement was the result of close collaboration between specialists in microbiology, oncology, and immunology.
He pointed out that working with Bifidobacterium bacteria was a major challenge, as they grow slowly and require an anaerobic environment, and the genetic tools available to study and modify them are limited compared to E. coli bacteria, which made developing this therapeutic approach more complicated.
Despite the promising results, the study confirms that the treatment has not yet been tested on humans, and the next stages will need to assess its long-term safety, the possibility of delivering it orally instead of by injection, study the durability of the immune response, and test its combination with new treatments such as KRAS inhibitors.
This research is part of a growing scientific trend known as "bacteria as medicine," where microorganisms are harnessed to deliver treatments directly to intractable tumors, opening the door to a new generation of precise and effective treatments with fewer side effects.
