Scientists have discovered that a genetically engineered version of a common gut bacteria, called Bifidobacterium longum, could help boost the body’s immune response against cancer when used alongside standard treatments. This research, led by teams from Tokushima University, Hiroshima University, and Hamamatsu University in Japan, introduces a new type of oral cancer vaccine that works as part of a combined immunotherapy approach. The bacteria was modified to display a larger portion of a protein called WT1, which is found in some cancers. The modified bacteria, named B440, was tested in a small Phase I clinical trial involving 12 patients with advanced bladder cancer who had already tried standard treatments without success. In six of these patients, the vaccine helped strengthen their preexisting immune response to WT1, and these patients stayed free of cancer progression for longer compared to the others. In the remaining six patients, the vaccine triggered a new immune response to WT1. After the trial, seven patients also received an additional cancer treatment called pembrolizumab. In three of these patients, the combination of B440 and pembrolizumab resulted in tumor shrinkage. These findings suggest that B440 may work more as a booster of the immune system rather than a standalone treatment. If further research confirms these results, a weak preexisting immune response to WT1 could serve as a useful marker to identify patients who might benefit the most from B440 or similar cancer immunotherapies. Only one side effect was reported—a mild, temporary increase in a protein called interleukin-6 (IL-6) in three patients. Dr. Shirakawa Toshiro, a cancer researcher at Kobe University, explained that this research is a step toward finding safer ways to enhance the body’s natural ability to fight cancer, especially when combined with other treatments like immune checkpoint inhibitors. Most existing oral vaccines today are designed to prevent infections, not cancer, and developing a safe and effective oral vaccine platform that can deliver cancer-related proteins to the gut’s immune system has been a major challenge. However, the researchers caution that this study was small and did not include a control group, so the results should be considered preliminary and needing further confirmation. A larger Phase I/II trial is now underway to test B440 in combination with two other cancer drugs, nivolumab and ipilimumab, for patients with a type of lung cancer called malignant pleural mesothelioma. According to Dr. Shirakawa, this work represents an important advance in exploring oral cancer vaccines as a new part of combination cancer immunotherapy. The study’s findings were published in the journal JCO Oncology Advances.