Early clinical study detects an immune response in half of participants and identifies a potential marker for determining who may benefit from the treatment
Written by Mona Khalil
The use of genetically modified bacteria in the development of cancer vaccines opens new possibilities for strengthening the immune system’s ability to fight tumors. An early clinical trial has shown that an experimental oral vaccine can stimulate an immune response directed against a cancer-associated protein in some patients.
Researchers tested the oral vaccine, known as B440, in a Phase I trial involving 12 patients with metastatic urothelial cancer whose disease had progressed after standard treatments. The initial results showed that the vaccine was generally well tolerated, while immune findings warranted larger studies to assess its effectiveness.
How do the modified bacteria work?
The approach uses Bifidobacterium longum, a bacterium found in some probiotic products, genetically modified to deliver part of a protein called WT1 (Wilms tumor 1), which is associated with several types of cancer. The aim is to activate immune cells against cancer cells.
The approach seeks to make use of gut-associated lymphoid tissue, which plays a role in regulating immune responses. This allows the cancer-associated antigen to be presented to the immune system through the digestive tract rather than by injection.
This research comes amid challenges facing current immunotherapies. Some tumors can evade immune surveillance, while some patients do not respond sufficiently to drugs that target immune checkpoints—mechanisms that act as natural brakes on immune activity.
An immune response in six patients
The study involved researchers from Kobe University in Japan, including Toshiro Shirakawa. They detected a cellular immune response directed against WT1 in six of the 12 patients who participated in the trial.
The six patients who showed an immune response had already demonstrated a weak response to the antigen before receiving the vaccine. This response was also associated with a longer period without disease progression compared with the other participants.
By contrast, the vaccine did not clearly generate a new detectable immune response in the six patients who had not shown a detectable response to the protein before treatment.
These findings suggest that a pre-existing immune response to the antigen could potentially serve as a biomarker to help identify patients who may benefit most from this type of vaccine in the future. However, this possibility still needs to be confirmed in larger studies.
Preliminary findings require further evaluation
Regarding safety, the treatment was generally well tolerated. Three patients experienced a temporary increase in levels of interleukin-6 (IL-6), a molecule involved in regulating inflammation. According to the study, all cases were mild and non-serious.
The findings were published in JCO Oncology Advances on July 7, 2026.
Despite these encouraging signs, the trial remains at an early Phase I stage, which focuses primarily on evaluating safety and tolerability and identifying preliminary signs of immune activity. The current findings are not sufficient to establish the vaccine’s effectiveness in treating cancer or support its widespread use. Larger clinical trials are needed to determine its potential benefit and identify the patients most likely to respond.
