Laboratory setup at JAIST where researchers cultivated the AUN bacterial system for preclinical trials.

Revolutionary ‘AUN’ Bacterial Therapy Kills Cancer Without Relying on the Immune System

By Harshit
Tokyo, Japan | November 10, 2025 | 10:30 AM JST

In a landmark breakthrough that could reshape the future of cancer treatment, scientists in Japan have developed a bacterial therapy that destroys tumors without depending on the immune system — a major step forward for patients whose immunity is compromised by chemotherapy or radiation.

The innovative therapy, known as AUN, was developed by a team led by Professor Eijiro Miyako at the Japan Advanced Institute of Science and Technology (JAIST), in collaboration with Daiichi Sankyo Co., Ltd. and the University of Tsukuba. Their findings were published this week in Nature Biomedical Engineering.


A 150-Year-Old Idea Reimagined

The use of bacteria to fight cancer is not new. The concept dates back to 1868, when German physician Busch observed cancer remission in a patient infected with bacteria. Later, in 1893, American surgeon Dr. William Coley experimented with bacterial injections — a therapy that laid the foundation for modern immunotherapies like checkpoint inhibitors and CAR-T cell treatments.

However, traditional immunotherapies share one major flaw: they require a strong immune system to be effective. For cancer patients undergoing aggressive chemotherapy or radiation, the immune response is often too weak for these therapies to succeed.

That’s where the AUN bacterial system stands apart — it attacks cancer cells directly, even when the body’s immune defenses are down.


Inside the AUN System: Two Bacteria Working in Harmony

The therapy’s name, AUN, comes from the Japanese concept of harmony between opposites — and that balance is at the core of this treatment.

The system consists of two bacterial species working together:

  1. Proteus mirabilis (A-gyo) — a naturally occurring bacterium that tends to thrive inside tumors.
  2. Rhodopseudomonas palustris (UN-gyo) — a photosynthetic bacterium that regulates and stabilizes the system.

Together, these microbes create a self-regulating ecosystem that seeks out and destroys tumors while protecting the body from harmful side effects.


How It Works: A Precision Attack on Tumors

The AUN therapy functions through a remarkable sequence of biological events:

  • Tumor targeting: A-gyo bacteria selectively infiltrate tumor tissue, drawn by its unique chemical environment.
  • Vascular destruction: Once inside, they damage the tumor’s blood vessels, starving it of oxygen and nutrients.
  • Shape transformation: A-gyo undergoes a process called filamentation, triggered by tumor-specific metabolites, enhancing its cancer-killing capacity.
  • Dynamic bacterial ratio: Inside the tumor, the bacterial balance shifts from an initial 3:97 ratio (A-gyo to UN-gyo) to nearly 99:1, boosting its therapeutic potency.
  • Toxicity control: UN-gyo acts as a stabilizer, reducing harmful inflammation and preventing cytokine release syndrome (CRS) — a common, sometimes fatal side effect of immune-based therapies.

The result: a highly efficient, immune-independent attack that leaves healthy cells largely unharmed.


Beyond Immunotherapy: Why AUN Is a Game Changer

Most cancer immunotherapies — from PD-1 inhibitors to CAR-T cells — rely on activating or modifying a patient’s immune cells to destroy cancer. These approaches are ineffective when immunity is weak, such as after chemotherapy or in late-stage disease.

AUN bypasses this problem completely. By operating outside the immune system, it works even in patients with severely compromised immunity.

Moreover, because the system is self-limiting — with one bacterium checking the other — it maintains safety and minimizes collateral damage. The researchers reported no major toxicity or uncontrolled inflammation in preclinical animal trials.


The Harmony of AUN: Science Meets Philosophy

Professor Miyako explains that the term “AUN” symbolizes more than just the names of the two bacteria. It represents the balance of aggression and control, destruction and preservation — a principle deeply rooted in Japanese culture and Buddhist philosophy.

“In our system, A-gyo attacks the tumor, while UN-gyo keeps it in check,” Miyako said. “Only together do they achieve harmony — efficient killing with minimal harm. That’s why we call it AUN.”

This cooperative relationship not only ensures safety but also enhances the bacteria’s ability to adapt to the tumor’s chemical environment — a hallmark of the therapy’s precision.


Toward Clinical Trials and Commercialization

The research team is now preparing for human clinical trials, aiming to bring AUN therapy into hospitals within the next six years.

“We are establishing a startup to develop this technology further,” Professor Miyako revealed. “Our goal is to move from preclinical validation to human trials as soon as possible. A new chapter in bacterial cancer therapy — pursued for over 150 years — is finally beginning.”

If successful, AUN could revolutionize cancer care for millions of patients who cannot benefit from immune-based treatments.


A Safer Future for Cancer Therapy

The implications extend beyond oncology. By controlling bacteria in a living system with such precision, scientists are opening the door to a new generation of “living medicines” — therapies that adapt dynamically to the body’s environment.

Unlike traditional drugs or immune therapies that can trigger dangerous overreactions, AUN appears to offer a safer, smarter, and more sustainable alternative.


Expert Perspectives

Dr. Takashi Sato, an immunologist unaffiliated with the study, called the development “a breakthrough in therapeutic bioengineering.”

“For decades, we’ve tried to weaponize the immune system against cancer, but this takes a different path entirely,” Sato said. “Using a bacterial partnership that can act independently of immunity could help patients whose bodies can no longer sustain immune-based treatments.”

He added that further testing will be needed to confirm long-term safety, particularly in humans, but praised the system’s ingenuity and adaptability.


Looking Ahead

As the global cancer burden continues to rise — with nearly 10 million deaths per year according to the World Health Organization — the need for innovative, efficient, and accessible treatments has never been greater.

If clinical trials confirm its promise, AUN bacterial therapy could offer new hope to patients for whom standard immunotherapies fail — marking the beginning of a new era in cancer medicine that combines nature, science, and balance in a way never seen before.

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