Colorectal cancer (CRC) is one of the leading causes of cancer-related death and remains a significant global health challenge. According to the American Cancer Society (ACS), there will be more than 150,000 new colorectal cancer diagnoses in the U.S. in 2026, with more than 55,000 deaths. [1]
Cancer vaccines have emerged as a promising immunotherapy for long-term tumor control. While Listeria monocytogenes (Lm)-based intravenous vaccines can generate tumor-reactive CD8 T-cells, clinical trial success has, so far, been limited. Researchers at Stony Brook University in New York, NY, conducted a study to determine whether in vivo targeting of gastrointestinal tissues via foodborne delivery of Lm-based cancer vaccines could control tumor growth in murine models of CRC.
Brian Sheridan, Ph.D., Photo courtesy: © 2026 Stony Brook Medicine. Used with permission.Scientists investigating the use of Listeria monocytogenes have discovered a way to build a modified version of Listeria as an oral vaccine to prime the immune system directly in the gut, where anti-tumor cells are then generated.
Details of the work, led Brian Sheridan, Ph.D., Associate Professor in the Department of Microbiology and Immunology in the Renaissance School of Medicine (RSOM) at Stony Brook University, a research scientist in the Stony Brook Cancer Center, and the senior author, are published in the Journal for the ImmunoTherapy of Cancer.[2]. Their work was supported, in part, with 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.
A patient’s own immune system
Cancer immunotherapy represents a treatment strategy that harnesses a patient’s own immune system to combat cancer. Immunotherapies are used to treat a small proportion of colorectal cancers. However, most colorectal cancers are not responsive to current immunotherapies.
Listeria monocytogenes is a bacterium that can cause infection, but its promise as an immunotherapy for several types of cancer, including colorectal cancer, has advanced to preclinical and clinical trials.
A different approach
This new research, using a murine model of colorectal cancer, is different from previous Listeria monocytogenes vaccine approaches, which were administered intravenously. The method used an oral delivery approach to generate a robust anti-tumor CD8 T-cell response in gastrointestinal tissues. Additionally, the method also provides a more targeted approach than traditional immunotherapy methods as the vaccine directly targets the gut and intestinal tissue where colorectal cancer emerges.
According to Sheridan, the research team engineered a highly attenuated strain of the bacterium by removing key virulence genes but allowing access to the intestinal immune system. This enabled them to stimulate an anti-tumor response without causing Listeriosis.
In mouse models, the vaccine remained confined to intestinal tissues and did not spread to other organs or cause significant side effects, such as weight loss. This localized approach ensured that the model subjects’ immune systems reacted only where the cancer develops, effectively targeting colorectal cancer cells. This process also minimized damage to healthy off-target tissues.
“The clinical significance of our laboratory findings is underscored by the vaccine performance in treating established tumors,” Sheridan 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,” he explained.
Furthermore, the method demonstrated that oral immunization combined with immune checkpoint inhibitors led to 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.
“Ultimately, such a strategy could significantly improve the prognosis for patients with advanced or metastatic colorectal cancer who have limited therapeutic options otherwise,” emphasizes Sheridan.
“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,” Sheridan concluded.
Reference
[1] Key Statistics for Colorectal Cancer. American Cancer Society (ACS). Online. Last accesses in February 2026.
[2] Lei X, Yu Y, Chung C, Qiu Z, Zhang Y, Chu TH, Li X, Yang R, Ozler KA, Burgac M, Westcott PMK, Beyaz S, Sheridan BS. Oral immunization with Listeria monocytogenes vaccine enhances immunotherapy for protective immunity in murine models of colorectal cancer. J Immunother Cancer. 2026 Feb 5;14(2):e011570. doi: 10.1136/jitc-2025-011570. PMID: 41644269; PMCID: PMC12878199.
Featured image: By modifying the bacterium Listeria monocytogenes, researchers are developing a promising vaccine against colorectal cancer. Photo courtesy: 2016 – 2026 © CDC/Unsplash license. Used with permission.
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