Challenging Over 150 Years of Immunotherapy: Scientists Unveil New Weapon That Kills Cancer Without the Immune System

Two bacteria working in harmony show powerful antitumor effects. The approach could transform treatment for immunocompromised patients.

A research team led by Professor Eijiro Miyako at the Japan Advanced Institute of Science and Technology (JAIST), working in collaboration with Daiichi Sankyo Co., Ltd. and the University of Tsukuba, has created a pioneering bacterial therapy for cancer that operates independently of the immune system. This new approach relies on a specially designed microbial consortium called AUN.

The concept of bacterial cancer therapy dates back to 1868, when German physician Busch reported that intentionally infecting a patient with bacteria led to tumor regression. Later, in 1893, Dr. William Coley proposed bacterial injections as a treatment, laying the foundation for cancer immunotherapy. Over the past 150 years, these early ideas evolved into advanced treatments such as checkpoint inhibitors and CAR-T cells. While effective for some, these therapies all depend on immune cell activity, which limits their effectiveness in patients whose immune systems are weakened by chemotherapy or radiotherapy.

The new AUN therapy overcomes this challenge by combining two naturally occurring bacterial strains:

• Proteus mirabilis (A-gyo), a microbe that thrives within tumors
• Rhodopseudomonas palustris (UN-gyo), a photosynthetic bacterium

Mechanisms of tumor eradication

Working in close cooperation, the “AUN” bacterial pair achieved remarkable tumor clearance in both mouse and human cancer models, even under immunocompromised conditions—all without relying on immune cells. The therapy demonstrated strong biocompatibility and very limited side effects, notably preventing cytokine release syndrome (CRS).

In this study, AUN’s potent antitumor activity was driven by several coordinated bacterial mechanisms, including:

• Precise targeting and destruction of tumor vasculature and cancer cells
• Structural transformation of A-gyo (filamentation) induced by tumor metabolites, which increased its cancer-fighting capacity
• Dynamic intratumoral population shifts, where the initial bacterial ratio of A-gyo : UN-gyo ≈ 3:97 rapidly changed to 99:1 within the tumor microenvironment
• Reduced pathogenicity and minimized side effects, including effective prevention of CRS

  

Harmony between bacterial partners

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.

Reference: “Tumour-resident oncolytic bacteria trigger potent anticancer effects through selective intratumoural thrombosis and necrosis” by Seigo Iwata, Taisei Nishiyama, Matomo Sakari, Yuki Doi, Naoki Takaya, Yusuke Ogitani, Hiroshi Nagano, Keisuke Fukuchi and Eijiro Miyako, 5 August 2025, Nature Biomedical Engineering.
DOI: 10.1038/s41551-025-01459-9

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