Oral Vaccine Candidate Using Modified Listeria Bacterium Shows Promise Against Colorectal Cancer in Early Tests

Researchers at Stony Brook University have developed an oral vaccine candidate based on a genetically modified, attenuated strain of Listeria monocytogenes. This vaccine stimulates powerful anti-tumor immune responses directly in the gut.

Led by immunologist Brian Sheridan, PhD, the research shows that the vaccine generates tumor-specific CD8+ T cells in the gastrointestinal tract.

In mouse models of colorectal cancer, the oral vaccine significantly improved tumor control, especially when combined with immune checkpoint inhibitors. This combination increases the infiltration of cancer-killing T cells into tumors.

Published on February 5, 2026, in the Journal for ImmunoTherapy of Cancer, the study presents a potential new strategy to overcome immunotherapy resistance in colorectal cancer, which is one of the leading causes of cancer-related deaths worldwide.

"The clinical significance of our laboratory findings is underscored by the vaccine performance in treating established tumors," says Dr. Sheridan. "While this vaccine alone initially curtailed local tumor growth, its true potential was revealed when combined with existing immune checkpoint inhibitors."

"This combination therapy led to profound tumor control in the model and suggests that the vaccine can effectively 'turn on' the immune system in tumors that were previously resistant to standard immune therapy," he explained in a press release.

Furthermore, the method demonstrated that oral immunization combined with immune checkpoint inhibitors induced the accumulation of tumor-specific CD8 T cells within the tumor microenvironment. These specialized immune cells remain stationed in the gut and provide immediate and long-lasting protection against cancer cells, a response not achieved by vaccination or immune checkpoint inhibitors alone. 

While the results are promising in preclinical models, human trials will be necessary to assess safety and efficacy.