A research team led by Professor Eijiro Miyako of the Japan Advanced Institute of Science and Technology (JAIST), in collaboration with Daiichi Sankyo Co., Ltd. and the University of Tsukuba, has developed a groundbreaking immune-independent cancer therapy. This therapy utilizes a novel microbial consortium named AUN, composed of the bacteria Proteus mirabilis (A-gyo) and Rhodopseudomonas palustris (UN-gyo). The study, published in Nature Biomedical Engineering, marks a paradigm shift in cancer treatment by overcoming the reliance on immune cells, which limits previous immunotherapies such as checkpoint inhibitors or CAR-T cells.
The history of cancer immunotherapy began in 1868 with the observation that bacterial infections could cause tumors to regress in rare cases. William Coley specifically utilized this idea in 1893 by employing bacteria for cancer treatment. Since then, over 150 years, immunotherapies have evolved into highly sophisticated methods, but they depend on a functional immune system. For patients with weakened immune systems—for instance, due to chemotherapy or radiation therapy—these approaches are often ineffective. The AUN therapy breaks through this barrier.
The AUN therapy is based on the synergistic collaboration of two bacteria: Proteus mirabilis (A-gyo) specifically colonizes tumors, while Rhodopseudomonas palustris (UN-gyo), a photosynthetic bacterium, acts as a regulatory partner. Together, they selectively destroy tumor vasculature and cancer cells without relying on immune cells. In preclinical studies using mouse and human cancer models, AUN demonstrated exceptional anti-tumor efficacy, even in immunocompromised environments. Particularly noteworthy is the minimal side effect rate, including the suppression of cytokine release syndrome, a common complication of immune-based therapies.
The efficacy of AUN relies on several mechanisms: A-gyo undergoes a structural transformation (filamentation) within the tumor microenvironment, triggered by tumor metabolites, which enhances its cytotoxic effect. Simultaneously, an intratumoral population shift—from an initial bacterial ratio of 3:97 (A-gyo to UN-gyo) to 99:1—leads to optimized tumor combat. UN-gyo, in turn, regulates the pathogenicity of both bacteria, minimizes side effects, and enhances tumor-specific cytotoxicity. This interplay, inspired by the Japanese concept of “AUN” (harmony of opposites), enables precise and effective tumor destruction.
The study highlights the high biocompatibility of the therapy, setting it apart from conventional approaches. Professor Miyako emphasized plans to establish a startup to translate the therapy into clinical trials within six years. This approach could offer new hope, particularly for immunocompromised patients for whom conventional immunotherapies fail.
The research findings, published on August 5, 2025, in Nature Biomedical Engineering, open a new chapter in bacteria-based cancer therapy. They not only challenge established immunotherapeutic approaches but also offer a promising alternative for treating cancer in difficult clinical scenarios.
The research findings were published online on August 5, 2025, in Nature Biomedical Engineering .
