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Sun Nyunt Wai
Photo Credit: Mattias Pettersson
Scientific Frontline: "At a Glance" Summary
- Discovery of Anti-Tumor Toxin: The purified cytotoxin MakA, secreted by the cholera bacterium Vibrio cholerae, has been identified as an agent that significantly inhibits the growth of colorectal cancer tumors.
- Mechanism of Action: MakA accumulates specifically within tumor tissue, inducing cancer cell death and suppressing proliferation while simultaneously recruiting innate immune cells, such as macrophages and neutrophils, to the tumor microenvironment.
- Safety and Specificity: In murine models, systemic administration of MakA targeted tumors locally without causing harmful systemic inflammation, weight loss, or organ dysfunction, indicating a high degree of specificity for cancerous tissue.
- Immune Modulation: The toxin alters the cellular composition of the tumor environment, stimulating the production of immune mediators that promote apoptosis while preserving regulatory mechanisms to protect surrounding healthy tissue.
- Therapeutic Potential: This study highlights a novel therapeutic avenue utilizing bacterial toxins to both directly target cancer cells and enhance the host's immune response, offering a potential alternative to traditional treatments like chemotherapy and radiation.
A toxin secreted by cholera bacteria can inhibit the growth of colorectal cancer without causing any measurable damage to the body. This is shown by a new study by researchers at Umeå University, Sweden. Systemic administration of the purified bacterial substance changes the immune microenvironment in tumors, and the results may open the way for research into a new type of cancer treatment.
"The substance not only kills cancer cells directly. It reshapes the tumor environment and helps the immune system to work against the tumor without damaging healthy tissue," says Sun Nyunt Wai, professor at Umeå University and one of the lead authors behind the study.
Colorectal cancer, i.e. cancer of the colon and rectum, is the third most common form of cancer in the world and the cancer with the second highest mortality rate globally. Today, cancer is usually treated with surgery, radiation, or chemotherapy. While it is effective in many cases, those methods also have significant side effects. Colorectal cancer is also increasing in the world. Therefore, it is valuable to find alternative treatment methods.
The researchers in Umeå have studied the cancer-inhibiting properties of the purified substance MakA, a so-called cytotoxin secreted by the cholera bacterium Vibrio cholerae. In experiments with mice, it was possible to see that systemic administration of MakA significantly reduced the growth of the tumors.
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| Saskia Erttmann Photo Credit: Mattias Pettersson |
The substance accumulated specifically in the tumor tissue, where it increased cell death of tumor cells and reduced their ability to increase in number. In parallel, MakA changed the composition of the cellular environment in tumors and increased the number of innate immune cells, especially macrophages and neutrophils, which in turn contributed to inhibiting tumour growth.
The treatment did not lead to any harmful inflammation in mice. No adverse effects on body weight, general health, or the function of vital organs could be seen even after repeated dosing. This suggests that the effect of MakA is local and specifically targeted at tumors.
Further analyses confirmed that MakA stimulated the formation of so-called immune mediators in the tumor that promote cell death while maintaining regulatory mechanisms that limit damage to surrounding tissue.
"Although more research is needed, the results clearly show an interesting path for developing a new type of cancer treatment, which utilizes substances that bacteria create to both kill cancer cells and strengthen the body's own defenses," says Saskia Erttmann, one of the lead authors behind the study.
The researchers emphasize that more studies are needed to explore the anti-cancer potential of MakA in other models as well as to assess its suitability for future clinical use.
Funding: The research has been funded by the Swedish Research Council, the Swedish Cancer Society and the Kempe Foundation.
Published in journal: Cell Death & Disease
Title: A bacterial toxin as a novel anti-cancer drug modulating the tumor-microenvironment
Authors: Lingyu Li, Pauline Evain, Michael Timothy Phillips, Maria Lopez Chiloeches, Anna Bergonzini, Teresa Frisan, Sun Nyunt Wai, and Saskia Friederike Erttmann
Source/Credit: Umeå University | Ola Nilsson
Reference Number: ongy011426_01
