An oral vaccine candidate, developed by researchers at Stony Brook University, is showing promise in boosting the immune system’s response to colorectal cancer, particularly in patients who do not respond to conventional immunotherapy. The vaccine, built upon a modified strain of the bacterium Listeria monocytogenes, is designed to stimulate a powerful immune response directly within the gut.
The research, published February 5, 2026, in the Journal for ImmunoTherapy of Cancer, details a novel approach to cancer treatment that focuses on priming the immune system in the gastrointestinal tract, the primary site of colorectal cancer development. Colorectal cancer is a leading cause of cancer-related death globally, with the American Cancer Society projecting over 150,000 recent cases and more than 55,000 deaths in the United States alone this year.
Immunologist Brian Sheridan, PhD, associate professor in the Renaissance School of Medicine at Stony Brook University and senior author of the study, explained that the team engineered a weakened version of Listeria, removing genes responsible for causing illness while preserving its ability to interact with the intestinal immune system. This modified bacterium acts as a delivery vehicle, triggering an anti-tumor response without causing listeriosis.
Previous attempts to utilize Listeria monocytogenes as a cancer vaccine vector have primarily involved intravenous delivery. This new research diverges from that approach, focusing on oral administration to generate a robust anti-tumor CD8 T cell response within the gastrointestinal tissues. “The clinical significance of our laboratory findings is underscored by the vaccine performance in treating established tumors,” Sheridan said in a press release. “While this vaccine alone initially curtailed local tumor growth, its true potential was revealed when combined with existing immune checkpoint inhibitors.”
In preclinical models, the oral vaccine remained localized within the intestinal tissues, avoiding spread to other organs and minimizing side effects like weight loss. This targeted approach ensures the immune system reacts specifically where the cancer develops, minimizing damage to healthy tissues. The study demonstrated that oral immunization, when coupled with immune checkpoint inhibitors, induced the accumulation of tumor-specific CD8 T cells within the tumor environment. These specialized immune cells provide immediate and long-lasting protection against cancer cells, a response not achieved through vaccination or immune checkpoint inhibitors alone.
The research suggests the vaccine can effectively “turn on” the immune system in tumors previously resistant to standard immunotherapy. “This combination therapy led to profound tumor control in the model,” Sheridan stated. The use of immunotherapies has transformed treatment for some cancer types, but the majority of colorectal cancers do not respond to currently approved immune checkpoint inhibitors.
The study was supported by funding from the Department of Defense, the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID), the Research Foundation for the State University of New York, and several charitable foundations. Sheridan emphasized that the method could significantly improve the prognosis for patients with advanced or metastatic colorectal cancer who have limited therapeutic options and potentially pave the way for a new generation of cancer vaccines that could both prevent disease onset and enhance the efficacy of existing immunotherapies.
