A bacterium from the intestines of Japanese tree frogs eliminated colorectal tumors in mice after a single intravenous injection. Researchers at Japan Advanced Institute of Science and Technology (JAIST) demonstrated in the journal Gut Microbes that Ewingella americana made all treated animals with colorectal cancer tumor-free and outperformed standard immunotherapy and chemotherapy. Several developmental steps remain before application in humans, but the mechanism is scientifically unusual.
A bacterium from the frog gut
The research team led by Prof. Eijiro Miyako examined 45 bacterial strains from the digestive tracts of Japanese tree frogs (Dryophytes japonicus), fire-bellied newts and lizards. Nine strains showed tumor-suppressive properties. E. americana was the most effective among them. The bacterium is known in microbiology as a facultative anaerobe: it survives in both oxygen-rich and oxygen-poor environments. This characteristic proved crucial for its anti-tumor activity.
How the bacterium attacks tumors
Tumor tissue is particularly vulnerable to E. americana for several reasons. It is poorly perfused and therefore oxygen-poor. Cancer cells suppress the immune system through the surface protein CD47. Tumor blood vessels are unusually leaky, allowing bacteria to penetrate more easily. These three factors together create an environment where the bacterium can multiply dramatically, while it barely survives in healthy tissue.
In the JAIST study, E. americana accumulated approximately 3,000-fold in tumor tissue within 24 hours of intravenous administration. The blood half-life was approximately 1.2 hours, after which the bacterium was virtually undetectable in the bloodstream.
The mechanism is twofold. On one hand, E. americana directly destroys tumor cells. On the other, it activates the immune system: the bacterium recruits T cells, B cells and neutrophils that secrete pro-inflammatory molecules (TNF-alpha and IFN-gamma), triggering further cancer cell death.
The result: complete tumor regression in all treated mice with colorectal cancer, a complete response rate of 100 percent. Compared to anti-PD-L1 immunotherapy and liposomal doxorubicin, a common chemotherapy drug, E. americana was superior in both metrics. After a 60-day observation period, no long-term toxicities occurred. Animals showed only transient mild inflammatory responses that normalized within 72 hours.
In comparison: bacterial cancer therapy has a history
The finding sounds novel but stands in a long research tradition. William Coley, a bone sarcoma surgeon at Memorial Hospital in New York, treated cancer patients beginning in 1891 with a mixture of inactivated Streptococcus bacteria and Serratia marcescens, the so-called Coley toxins. The therapy triggered immune responses that led to tumor regression in some patients. It fell into obscurity as radiation and chemotherapy came to the fore.
The only bacterium-based cancer therapy currently approved clinically is BCG (Bacillus Calmette-Guérin, an attenuated tuberculosis bacterium). It has been used successfully for decades in non-invasive bladder cancer and is considered standard treatment after tumor removal. Researchers at the Helmholtz Centre for Infection Research (HZI) are also investigating genetically engineered Salmonella typhimurium variants as potential cancer therapeutics.
Colorectal cancer is one of the most common cancers globally. The disease is spreading faster and affecting younger populations with each passing year. Researchers are urgently seeking new treatment approaches for advanced cases with distant metastases.
Three steps until clinical trials
A convincing mouse experiment is not clinical proof. For possible human application, typically three levels must be passed.
First: testing in larger animal models to assess safety and efficacy under more realistic conditions. Second: validation in human cancer cell lines, since tumor biology differs significantly between mice and humans. Third: a clinical phase 1 trial in humans. The JAIST team has not yet provided a timeline for any of these steps.
According to the Gut Microbes publication, the team plans to next test E. americana against breast cancer, pancreatic cancer and melanoma, as well as investigate dosing strategies and combination therapies with existing immunotherapies. How long the road from animal testing to clinical application can be is shown by BCG: from Coley's observations in 1891 to evidence-based cancer therapy took approximately 80 years. For E. americana, this path could be shorter because the tools of modern cancer research are more powerful. No timeline exists yet.