Scientists have genetically engineered bacteria that can activate the immune system – enabling them to attack cancer cells more aggressively. A researcher says that they would like to test this in human trials and explore how their bacterial therapy can be combined with established types of immunotherapy.
Researchers are now developing bacteria to combat cancer. Specifically, they have genetically engineered Escherichia coli to produce molecules that activate the immune system to attack cancer cells.
The researchers tested their bacteria on mice, and this substantially improved cancer responses, with some mice even being cured. Moreover, mice cured through this method could not develop the same type of cancer again, with the bacteria functioning as a vaccine.
The results have inspired the scientists to see great potential in using designer bacteria to combat cancer.
“We are eager to progress to human clinical trials and investigate how our bacterial therapy interacts with established types of immunotherapy. We expect to create synergy that can greatly improve outcomes for patients,” explains Morten Otto Alexander Sommer, Professor, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.
The research has been published in EMBO Reports.
Aiming to use bacteria to cure mice of cancer
There have long been indications that bacteria might be used in combatting cancer. For instance, clinical studies have shown that people who have cancer and higher concentrations of specific gut bacteria tend to respond better to treatment.
In the new study, the researchers took a different approach by genetically engineering E. coli to produce indole-3-acetate, which can activate the immune system’s aryl hydrocarbon receptors. These receptors are part of a signalling pathway that is critical to the immune response.
Bacterial production of indole-3-acetate should theoretically enhance the immune system’s ability to combat cancer. Previous research has also revealed that people with cancer with heightened activation of aryl hydrocarbon receptors in their tumours survived longer, since their immune response operates more effectively.
The researchers tested the genetically engineered E. coli on mice. They engrafted a tumour subcutaneously in each mouse, and once the tumour had become established, they injected the bacteria directly into it.
“The concept behind our experiment was for the bacteria to colonise the tumour environment and continuously produce molecules that activate the immune response to cancer. This method also activates the immune system locally and not in the entire body, with the bacteria consistently maintaining high immune activity within the tumour environment,” says Morten Otto Alexander Sommer.
Mice cured of cancer
This concept may seem theoretical, but the researchers demonstrated that it is feasible in practice. Tumours grew considerably less rapidly among mice with the genetically engineered E. coli injected directly into their tumours, with some mice even being cured.
The researchers subcutaneously engrafted a second tumour in mice previously cured. Remarkably, the cancer did not become established in any of these mice, since their immune systems successfully eliminated the cancer cells.
“This demonstrates that these E. coli can create a robust immune response against cancer. This also suggests that the immune system retains memory, enabling it to combat the cancer effectively if it recurs,” notes Morten Otto Alexander Sommer.
Aiming for human trials
Morten Otto Alexander Sommer explains that the research was conducted using a model for bowel cancer, but he expects that it could be effective against other types of cancer.
Morten Otto Alexander Sommer and colleagues aim to transition their promising experiments from mice to human trials. They are already discussing with several oncologists to explore possibilities and determine the appropriate methods for clinical trials that can validate their findings.
“Assessing risks will be a critical aspect of injecting bacteria directly into the human body. The bacteria we use are not pathogenic, but many people with cancer have compromised immune systems, which heightens their susceptibility to infection. We must therefore carefully regulate the quantity of bacteria administered to such people,” cautions Morten Otto Alexander Sommer.
Research can take several paths
In future research, Morten Otto Alexander Sommer aims to investigate how bacteria producing indole-3-acetate can be combined with established types of immunotherapy, such as immune checkpoint inhibitors.
He expects that these types of therapy could be synergistic, enhancing the immune system’s ability to attack cancer cells and delivering improved outcomes.
Finally, the researchers aim to explore the role of gut bacteria, which appear to influence how effective cancer therapy is by producing indole-3-acetate.
“This indicates that probiotics could be developed to promote these beneficial bacteria, thereby bolstering the immune system’s ability to defend the body against cancer. There are numerous fascinating avenues to explore regarding how bacteria could play a transformative role in cancer therapy,” concludes Morten Otto Alexander Sommer.
