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 (阿吽) (Figure 1).
Cancer immunotherapy originated in 1868 when the German physician Busch reported a case of a cancer patient who was intentionally infected with bacteria and subsequently cured. Since then, in 1893, Dr. William Coley proposed the use of bacteria for cancer treatment, and immunotherapies have been evolving into modern treatments such as checkpoint inhibitors and CAR-T cells for over 150 years. While powerful, these approaches 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. AUN is composed of two naturally occurring bacteria:
- Proteus mirabilis (A-gyo), a tumor-resident microbe
- Rhodopseudomonas palustris (UN-gyo), a photosynthetic bacterium
Working in perfect synergy, these "AUN" bacteria produce exceptional tumor eradication in both murine and human cancer models, even in immunocompromised environments—all without the help of immune cells (Figure 2a). The therapy exhibits high biocompatibility and minimal side effects, including suppression of cytokine release syndrome (CRS) (Figure 2b).
In this study, AUN exhibits transcendent antitumor effects through uniquely orchestrated bacterial mechanisms, including:
- Selective destruction of tumor vasculature and cancer cells
- Structural transformation of A-gyo (filamentation) triggered by tumor metabolites, enhancing its antitumor potency (Figure 3)
- 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
Notably, 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. This "cooperation of labor" mirrors the Japanese philosophical concept of "AUN"—perfect harmony between opposites. It is this delicate and dynamic interplay between the two bacterial species that unlocks the remarkable antitumor efficacy—a feat previously unattainable through conventional therapies.
"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. It offers a long-awaited therapeutic solution in cases where conventional immunotherapies fail—ushering in the dawn of truly immune-independent cancer treatment.
The research has been published online in Nature Biomedical Engineering on 5 August 2025 .
