The bacteria-delivered anti-cancer therapy directly to tumour cells, potentially outperforming the drug on its own.
A genetically engineered strain of E. coli could be the future of precision anti-cancer tools, infiltrating tumours and producing cancer drugs from within, according to researchers from Shandong University, China.
The research team modified a probiotic strain of Escherichia coli known as Nissle 1917 (EcN), enabling it to produce romidepsin (Istodax), an anti-cancer drug approved by the FDA for certain cancers which can cause significant side effects when delivered through the bloodstream. It is not approved by the Therapeutic Goods Administration.
When injected into mice with breast cancer, the bacteria were able to home in on tumours, colonise them and begin producing the drug directly within the cancer tissue, creating a dual-action therapy.
Instead of circulating throughout the body like traditional chemotherapy, the medication was largely confined to the tumour; while blood levels of romidepsin peaked at around 0.015ÎĽg/mL, concentrations inside tumours reached as high as 1.5ÎĽg per gram of tissue within six hours. Mice treated with the engineered bacteria showed slower tumour growth.
Interestingly, the engineered bacteria didn’t just match the efficacy of the drug – they appeared to outperform it at a molecular level, activating additional immune responses and suppressing tumour-promoting proteins, showing lower death rates than in mice given the medication through the traditional route.
The bacteria appeared to enhance the overall anti-cancer response. They not only halted cancer cell growth but also activated immune responses, increased tumour-suppressing proteins, reduced cancer-promoting genes and triggered multiple forms of cancer cell death.
Injecting romidepsin is known to damage healthy tissues, particularly the heart. However, when bacteria produced it inside the tumour, the drug accumulated with high specificity, much less entered the bloodstream and the side effects were reduced, the researchers explained.
The researchers also designed different bacterial strains with built-in “control systems.” Some required a chemical trigger to start producing the drug, while others switched on automatically in low-oxygen environments — a defining feature of many tumours. This allows for more precise control, ensuring the drug is released only where it’s needed.
Despite the promising results, the research is at a very early stage with no human trials yet and several challenges remain, including precisely controlling the drug production in the body, maintaining the genetic stability of the engineered bacteria, safely clearing the bacteria after treatment and ensuring consistent results across different cancers.
Still, the findings highlighted the potential of using engineered microbes as targeted cancer therapies – a strategy that could overcome one of the biggest limitations of conventional chemotherapy: delivering drugs precisely to tumours without harming the rest of the body, researchers explained.
They concluded that their findings could lay the groundwork for a new class of treatments in which living cells are programmed to seek out cancer and destroy it from within.
