A team of researchers in Japan has developed a bacterial therapy that can attack tumors without relying on the patient’s immune system, a potential benefit for individuals whose immunity is weakened by chemotherapy, radiation, or other conditions. Current immunotherapies such as CAR-T cells and checkpoint inhibitors depend on an intact immune response, making them unsuitable for many immunocompromised patients.

The work, led by scientists from the Japan Advanced Institute of Science and Technology (JAIST), Daiichi Sankyo, and the University of Tsukuba, involves a bacterial consortium called AUN. The therapy combines two naturally occurring bacteria: “Proteus mirabilis” (A-gyo), a tumor-resident bacterium with reduced motility and no pathogenicity, and “palustris” (UN-gyo), a photosynthetic bacterium that improves the safety and tumor-targeting properties of A-gyo. Administered intravenously at a ratio of 3:97 (A-gyo to UN-gyo), the bacteria preferentially accumulate in tumors.

Once established in the tumor, the bacteria cause intratumoral blood clotting, vascular collapse, platelet aggregation, and extensive tumor cell death. This process appears to involve the release of bacterial toxins and the formation of a dense biofilm within the tumor. In animal studies, these effects occurred without evidence of systemic toxicity or cytokine release syndrome.

In tests using mouse models of colorectal cancer, sarcoma, metastatic lung cancer, and drug-resistant triple-negative breast cancer—including models lacking functional immune cells—repeated doses of AUN produced high rates of complete tumor regression. The findings suggest that the therapy’s effect is driven by local vascular shutdown and direct cytotoxicity rather than immune-mediated mechanisms.

The bacteria are naturally occurring and not genetically modified, and their activity can be halted with antibiotics, giving the researchers a degree of control over treatment. However, the use of live bacteria in therapy raises questions about possible infection risks, drug resistance, and long-term safety. These issues will require further study before the therapy can advance to human trials.

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