A joint 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 University of Tsukuba, has developed a groundbreaking immune-independent bacterial cancer therapy using a novel microbial consortium called AUN. This revolutionary approach addresses a critical limitation in cancer treatment by providing therapeutic options for immunocompromised patients who cannot benefit from conventional immunotherapies.
Breaking the Immune Dependence Barrier
Cancer immunotherapy has evolved over 150 years since German physician Busch first reported a case of bacterial infection curing cancer in 1868, followed by Dr. William Coley's bacterial cancer treatment proposal in 1893. Modern immunotherapies including checkpoint inhibitors and CAR-T cells have shown remarkable efficacy, but they fundamentally depend on immune cells—making them ineffective for many cancer patients with compromised immune systems due to chemotherapy or radiotherapy.
The newly developed AUN therapy overturns this long-standing limitation by achieving exceptional tumor eradication in both murine and human cancer models, even in immunocompromised environments, without requiring immune cell assistance.
Synergistic Bacterial Partnership
AUN is composed of two naturally occurring bacteria working in perfect synergy:
- Proteus mirabilis (A-gyo): A tumor-resident microbe
- Rhodopseudomonas palustris (UN-gyo): A photosynthetic bacterium
The therapy exhibits high biocompatibility and minimal side effects, including suppression of cytokine release syndrome (CRS). UN-gyo functions as a regulatory partner only when coexisting with A-gyo, helping to suppress the pathogenicity of both strains while simultaneously enhancing their tumor-specific cytotoxicity.
Unique Mechanisms of Action
AUN exhibits transcendent antitumor effects through uniquely orchestrated bacterial mechanisms:
- Selective destruction of tumor vasculature and cancer cells
- Structural transformation of A-gyo (filamentation) triggered by tumor metabolites, enhancing its antitumor potency
- Functional optimization via intratumoral population shift—although the initial bacterial mixture is A-gyo : UN-gyo ≈ 3:97, it dramatically shifts to 99:1 within the tumor microenvironment
- Suppression of pathogenicity and minimization of side effects, including the avoidance of CRS
This "cooperation of labor" mirrors the Japanese philosophical concept of "AUN"—perfect harmony between opposites. The delicate and dynamic interplay between the two bacterial species unlocks remarkable antitumor efficacy previously unattainable through conventional therapies.
Clinical Translation and Future Outlook
"To accelerate the social implementation of this research, we are preparing to launch a startup and aim to begin clinical trials within six years," said Professor Eijiro Miyako, lead author of the study. "A new chapter in bacteria-based cancer therapy—pursued for over 150 years—is finally beginning."
This revolutionary approach represents a paradigm shift for immunocompromised cancer patients, offering a long-awaited therapeutic solution in cases where conventional immunotherapies fail. The research has been published online in Nature Biomedical Engineering on August 5, 2025, marking the dawn of truly immune-independent cancer treatment.
