A team of researchers led by Brian Sheridan, PhD, at Stony Brook University has developed a new oral vaccine strategy using the bacterium Listeria monocytogenes to help combat colorectal cancer. The study, published in the Journal for the ImmunoTherapy of Cancer, outlines how a modified version of Listeria can be used as an oral vaccine to stimulate an immune response directly within the gut.
Colorectal cancer is one of the most deadly cancers globally. The American Cancer Society estimates that there will be over 150,000 new cases and more than 55,000 deaths from colorectal cancer in the United States in 2026. While immunotherapy has been used for some patients with this disease, most do not respond to current treatments.
Listeria is known to cause infections but has also shown potential as an immunotherapy agent in pre-clinical and clinical trials for various cancers. Unlike earlier approaches that relied on intravenous delivery, this research tested an oral method using a mouse model. The goal was to generate strong anti-tumor CD8 T cell responses specifically within gastrointestinal tissues.
Dr. Sheridan explained that his team engineered a weakened strain of Listeria by removing key virulence genes while still allowing it access to the intestinal immune system. This approach aimed to trigger an anti-tumor response without causing listeriosis.
In their experiments with mice, the vaccine remained limited to intestinal tissues and did not spread or cause major side effects like weight loss. According to Dr. Sheridan: “The clinical significance of our laboratory findings is underscored by the vaccine performance in treating established tumors,” he said. “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.”
The study found that combining oral immunization with immune checkpoint inhibitors increased levels of tumor-specific CD8 T cells at tumor sites in the gut—a result not achieved through either treatment alone. These cells remained stationed in intestinal tissue and provided ongoing protection against cancer cells.
“Ultimately, such a strategy could significantly improve the prognosis for patients with advanced or metastatic colorectal cancer who have limited therapeutic options otherwise,” Dr. Sheridan emphasized. “Additionally, this method could pave the way for a new generation of cancer vaccines that could both prevent the onset of disease and enhance the efficacy of existing immunotherapies in clinical settings.”
The research involved scientists from Stony Brook’s Department of Microbiology and Immunology and Cold Spring Harbor Laboratory, supported by funding from several organizations including federal agencies and charitable foundations.
Stony Brook University News played a role in media coverage related to university research achievements (official website). It also supports journalists by offering access to experts and providing information about ongoing research (official website). In addition, Stony Brook University News assists journalists covering stories connected with Long Island and Manhattan locations (official website). Services include coordinating interviews and offering expert commentary on science topics such as health (official website). Its work focuses on communications within education (official website) from its Office of Communications and Marketing based at Stony Brook while supporting activities elsewhere (official website).