Scientists at the Japan Advanced Institute of Science and Technology (JAIST) have identified a naturally occurring bacterium from the intestines of the Japanese tree frog (Dryophytes japonicus) that shows significant anti-cancer activity in mice. The survey results are intestinal microorganismsHere we present a new approach to cancer treatment that uses live bacteria to directly target tumors, rather than simply altering the gut microbiome.
Unlike many previous studies that focused on changing the composition of gut bacteria or transplanting fecal microbiota, this study isolated individual bacterial strains, grew them in the lab, and administered them intravenously to attack tumors.
The research team collected 45 bacterial strains from the intestines of Japanese tree frogs, red-bellied newts (Cynops pyrrhogaster), and Japanese sow lizards (Takydromus tacodoromoides). After screening the bacteria for anti-cancer activity, nine strains were found to be promising. among them, American Ewingella produced the most powerful results.
One treatment removes tumors in mice
In a mouse model of colorectal cancer, American E It completely removes the tumor, resulting in a 100% complete response (CR) rate. The researchers said the treatment outperformed standard treatments used for comparison, including immune checkpoint inhibitors (anti-PD-L1 antibodies) and the chemotherapy drug liposomal doxorubicin.
Although the researchers stress that these findings are limited to mice, they believe the results provide a promising proof of concept for developing new bacterial cancer treatments.
Double attack on cancer cells
This bacterium appears to fight cancer through two complementary mechanisms.
beginning, American E Attacks the tumor directly. As a facultative anaerobic bacterium, it grows in both oxygen-rich and oxygen-poor environments and is capable of growing within anoxic regions commonly found within tumors. Once there, the number of bacteria increased by about 3,000 times within 24 hours of treatment, directly damaging the cancer cells.
Second, bacteria stimulate the immune system. Its presence attracted T cells, B cells, and neutrophils to the tumor. These immune cells released inflammatory signaling molecules such as TNF-α and IFN-γ, which enhanced the immune response and promoted cancer cell death.
Why do bacteria target tumors?
One of the most impressive discoveries was that American E It accumulated almost exclusively inside tumors and did not colonize healthy organs.
Researchers believe this tumor specificity is due to several factors working together.
- The hypoxic environment inside the tumor promotes bacterial growth.
- Cancer cells produce the CD47 protein. The CD47 protein suppresses local immune activity and creates conditions in which bacteria can survive.
- Tumor blood vessels are abnormally leaky, making it easier for bacteria circulating in the bloodstream to invade tumor tissue.
- Tumor-specific metabolic changes provide nutrients that support bacterial growth.
These properties allow bacteria to concentrate at tumor sites while avoiding normal tissue.
Good safety results
The research team also assessed the safety of the treatment.
They found that the bacteria were rapidly cleared from the bloodstream and became undetectable within 24 hours, with a half-life of about 1.2 hours. No bacterial colonization was detected in healthy organs such as the liver, spleen, lungs, kidneys, and heart.
The treatment caused only mild, temporary inflammation that returned to normal within 72 hours. During the 60-day observation period, researchers found no evidence of chronic toxicity.
Spread to other types of cancer
This study established proof of concept for using naturally occurring bacteria in cancer treatment. Future studies will examine whether this approach can also be applied to other solid tumors such as breast cancer, pancreatic cancer, and melanoma.
The team also plans to optimize the treatment through approaches such as dose fractionation and direct injection into the tumor. Researchers also American E It is even more effective when combined with existing chemotherapy or immunotherapy.
The findings also highlight the potential value of exploring biodiversity as a source of future medicine, offering the possibility of new treatment options for patients with difficult-to-treat cancers.
Glossary
- Facultative anaerobic bacteria: Bacteria can grow in both oxygen-rich and oxygen-poor environments and can grow selectively in the hypoxic conditions found within tumors.
- Complete response (CR): Complete disappearance of detectable tumors after treatment.
- Immune checkpoint inhibitors: Drugs that remove signals that cancer cells use to suppress the immune system, allowing T cells to more effectively attack tumors.
- CD47: A protein on the surface of cells that sends a signal to the immune system telling it not to eat. Many cancer cells produce large amounts of CD47 to avoid immune attack.
This research was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (A) (Project Number 23H00551), the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research Challenging Research (Pioneering) (Project Number 22K18440), and the Japan Society for the Promotion of Science’s Japan’s Top Research Universities Promotion Project (J-PEAKS). (Grant Number: JPJS00420230006), Japan Science and Technology Agency (JST) Startup Ecosystem Co-Creation Project (Grant Number: JPMJSF2318), JST SPRING (Grant Number: JPMJSP2102).
