Oral Vaccine Shows Promise in Combating Colorectal Cancer

A new strategy utilizing a modified bacterium, Listeria monocytogenes, as an oral vaccine is demonstrating potential in the fight against colorectal cancer. Researchers at Stony Brook University have engineered a version of the bacterium to stimulate the immune system directly within the gut, generating anti-tumor cells.

The Challenge of Colorectal Cancer and Immunotherapy

Colorectal cancer remains a significant global health challenge. The American Cancer Society projects over 150,000 new diagnoses and more than 55,000 deaths in the U.S. Alone in 2026. Although cancer immunotherapy—harnessing the body’s own immune system to fight cancer—holds promise, it is currently effective for only a small proportion of colorectal cancer patients. Most colorectal cancers do not respond to existing immunotherapies.

How the Oral Vaccine Works

Previous Listeria-based vaccine approaches for cancer were administered intravenously. This new research, published in the Journal for the ImmunoTherapy of Cancer, takes a different approach. The team, led by Stony Brook immunologist Brian Sheridan, engineered a highly attenuated strain of Listeria monocytogenes by removing key virulence genes. This allows the bacterium to access the intestinal immune system without causing illness (Listeriosis).

The oral delivery method generates a robust anti-tumor CD8 T cell response within gastrointestinal tissues. This targeted approach focuses the immune response directly on the gut, where colorectal cancer originates, minimizing damage to healthy tissues. In mouse models, the vaccine remained localized within the intestinal tissues and did not spread to other organs, nor did it cause significant side effects like weight loss.

Synergistic Effect with Immune Checkpoint Inhibitors

The vaccine’s true potential was revealed when combined with existing immune checkpoint inhibitors. While the vaccine alone initially slowed tumor growth, the combination therapy led to profound tumor control in the murine models. This suggests the vaccine can effectively “turn on” the immune system in tumors previously resistant to standard immunotherapy.

The research demonstrated that oral immunization, coupled with immune checkpoint inhibitors, induced the accumulation of tumor-specific CD8 T cells in 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.

Future Implications

“such a strategy could significantly improve the prognosis for patients with advanced or metastatic colorectal cancer who have limited therapeutic options otherwise,” emphasizes Sheridan. He also suggests this method could pave the way for a new generation of cancer vaccines capable of both preventing disease onset and enhancing the efficacy of existing immunotherapies.

This 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.