Columbia University researchers have engineered a novel cancer immunotherapy using probiotic bacteria to target and destroy cancer cells. This approach leverages the natural tumor-targeting properties of bacteria to deliver personalized cancer vaccines, showing promise in preclinical models of advanced cancers.
Personalized Microbial Cancer Vaccines
The engineered bacteria are designed to express neoantigens specific to an individual's tumor. "Every cancer is unique – tumor cells harbor distinct genetic mutations that distinguish them from normal healthy cells," said Nicholas Arpaia, PhD, Associate Professor of Microbiology & Immunology at Columbia University. By programming bacteria to target these cancer-specific mutations, the therapy stimulates a patient’s own immune system to detect and kill their cancer cells.
In mouse models of advanced colorectal cancer and melanoma, the bacterial vaccine significantly suppressed the growth of both primary and metastatic tumors, in many cases eliminating them entirely. Importantly, the treatment left healthy cells unharmed, highlighting its precision.
Mechanism of Action
The probiotic E. coli strain is genetically modified to precisely control its interaction with the immune system. These modifications include encoding neoantigens that train the immune system to target cancer cells expressing the same proteins. The engineered bacteria also counteract immunosuppressive mechanisms that tumors use to evade immune attacks.
According to Andrew Redenti, an MD/PhD student at Columbia University, "The important advantage of our system is its unique ability to coordinately restructure and activate all arms of the immune system to induce a productive antitumor immune response." This comprehensive immune activation is believed to be the reason for the system's effectiveness in advanced solid tumor models, which have been particularly difficult to treat with other immunotherapies.
Potential for Preventing Recurrence
The bacterial vaccine also demonstrated the ability to reduce cancer growth when administered before tumor development and prevented the regrowth of tumors in mice that had been cured. This suggests the vaccine may have the potential to prevent cancer recurrence in patients who have experienced remission.
Future Directions
The researchers are focused on further optimizing the safety of the engineered bacteria through additional genetic programming. The ultimate goal is to advance this therapy into human clinical trials. "As we continue to integrate additional safety optimizations through further genetic programming, we are getting closer to the point of testing this therapy in patients," says Arpaia.
Tal Danino, PhD, Associate Professor of Biomedical Engineering at Columbia's School of Engineering, notes that the manufacturing of bacterial strains can be quite fast, potentially reducing the time to treatment once a tumor is sequenced and its unique neoantigens are identified.
The study, titled "Probiotic neoantigen delivery vectors for precision cancer immunotherapy," was published in Nature.
