A research 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, has created an innovative cancer treatment that works without relying on the immune system. The new approach uses a unique microbial partnership known as AUN, forming the foundation of an immune-independent bacterial therapy.

The concept of bacterial cancer therapy dates back to 1868, when German physician Busch reported that a cancer patient deliberately infected with bacteria later experienced remission. In 1893, Dr. William Coley further advanced this idea by developing bacterial-based treatments, paving the way for modern immunotherapies such as checkpoint inhibitors and CAR-T cell therapies.

While these treatments have transformed cancer care, they share a major drawback: they depend heavily on the immune system. For patients whose immunity is weakened by chemotherapy or radiotherapy, such therapies often fail to work effectively.

AUN: Two Bacteria in Perfect Balance

The newly developed AUN therapy directly overcomes this limitation. It is made up of two naturally occurring bacterial species:

• Proteus mirabilis (A-gyo), a bacterium that naturally resides in tumors
• Rhodopseudomonas palustris (UN-gyo), a photosynthetic bacterium

Together, these bacteria act in harmony to destroy cancer cells in both animal and human models. Remarkably, they succeed even when immune function is impaired. AUN has shown strong compatibility with the human body and few side effects, including suppression of cytokine release syndrome (CRS), a potentially dangerous immune reaction.

How AUN Works to Eliminate Tumors

The AUN consortium achieves its tumor-fighting power through a series of coordinated mechanisms:

• Precisely targeting and destroying tumor blood vessels and cancer cells
• Undergoing a structural transformation in A-gyo (filamentation) triggered by tumor-specific metabolites, which enhances its ability to kill cancer cells
• Adjusting the bacterial ratio inside the tumor environment, shifting from an initial mix of roughly 3:97 (A-gyo to UN-gyo) to about 99:1, maximizing its therapeutic strength
• Reducing toxicity and minimizing side effects, including avoidance of CRS

Harmony Between Opposites

UN-gyo only becomes active and beneficial when paired with A-gyo, serving as a regulator that curbs harmful bacterial activity while increasing their cancer-killing precision. This mutual cooperation embodies the Japanese concept of “AUN,” symbolizing balance and harmony between opposites. It is this finely tuned relationship that gives the therapy its exceptional results, achieving what traditional immune-dependent treatments could not.

Toward Clinical Trials and a New Era in Cancer Therapy

“We are preparing to launch a startup to advance this technology and hope to begin clinical trials within six years,” explained Professor Miyako. “A new chapter in bacteria-based cancer therapy – pursued for over 150 years – is finally beginning.”

This groundbreaking method marks a turning point for cancer patients with weakened immune systems. It offers a long-sought option where conventional immunotherapies fall short, signaling the arrival of truly immune-independent cancer treatment.

The findings have been published in Nature Biomedical Engineering.