Scientists have developed a new method for treating cancer that relies on turning beneficial bacteria into "microfactories" for drugs inside tumors, so that they produce chemotherapy on-site, in conjunction with activating the immune system.
Experiments conducted on mice with colorectal cancer showed promising results; three out of seven tumors disappeared completely, and the growth of other tumors not directly targeted by the bacteria slowed.
Although the results are still preliminary, they open the door to the development of more precise treatments that target tumors while minimizing damage to healthy tissue.
One of the biggest problems in cancer treatment is the difficulty in distinguishing between cancerous cells and healthy tissue.
Chemotherapy can kill cancer cells, but it spreads throughout the body and can cause widespread side effects. Immunotherapy, which stimulates the immune system to attack tumors, can sometimes lead to the immune system attacking healthy tissue and causing infections and serious complications.
Therefore, scientists are looking for ways to deliver treatment directly to the tumor.
In the new study, a team led by immunologist Nicholas Arbaya of Columbia University used a strain of beneficial bacteria known as Escherichia coli Nissle 1917, a non-pathogenic strain used in some probiotic products.
Some types of bacteria are characterized by their ability to reach tumors and multiply within them, given that the tumor environment may be low in oxygen and rich in nutrients, with a relatively weak local immune response.
When scientists injected the bacteria into mice with colorectal tumors, they quickly disappeared from most organs, but accumulated inside the tumors. After five days, their numbers exceeded one billion bacterial cells per gram of tumor tissue.
After confirming the bacteria's ability to reach tumors, scientists modified its genes to produce an enzyme called "cytosine deaminase".
This enzyme converts the relatively low-toxicity substance 5-fluorocytosine (5-FC) into the drug 5-fluorouracil (5-FU), a widely used chemotherapy treatment for colorectal cancer.
Thus, the substance “5-FC” can be given to the body, and then converted into chemotherapy within the tumor where the bacteria are located, instead of spreading “5-FU” directly throughout the body.
But initial experiments revealed an unexpected problem: the bacteria were producing 5-FU, then destroying part of it themselves. This is due to a naturally occurring gene in E. coli bacteria known as preTA, which helps them break down the drug.
Scientists deleted these genes, which improved the effectiveness of the treatment.
Scientists did not stop at producing chemotherapy. They found that the treatment succeeded in activating immune cells that attack cancer, but it also stimulated tumors to develop mechanisms to resist the immune attack, including increasing levels of the immunosuppressive protein PD-L1.
"super-stimulator" of the "IL-15" protein, with the aim of activating anti-cancer immune cells, and a nanobody that blocks "PD-L1" and helps remove one of the barriers that tumors use to disable the immune system.
Thus, the modified bacteria came to work in three ways at the same time: producing chemotherapy within the tumor, activating the immune system, and disabling one of the tumor's mechanisms of resistance to immune attack.
When this approach was tested on mice, combining these mechanisms led to better results than using bacterial chemotherapy or bacterial immunotherapy alone.
Three out of seven tumors disappeared completely, representing 43%.
Interestingly, the effect was not limited to the tumors that received direct treatment. Scientists implanted tumors on both sides of some mice's bodies, treated only one tumor, but the growth of the other tumor also slowed, even though it did not contain the modified bacteria.
Scientists believe this result indicates that the treatment stimulated a broader immune response against cancer.
However, there is still a long way to go before this treatment can be tested on humans. The study was conducted on mice with a limited number of tumors, and the experiments involved injecting the bacteria directly into the tumor, a method that may not be suitable for all patients or types of cancer.
Scientists need to test the approach in more complex models that mimic human cancers, as well as develop safe and effective ways to deliver the bacteria to tumors.
However, the study presents a new idea for cancer treatment, based on using live bacteria to deliver chemotherapy directly to the tumor, while simultaneously stimulating the immune system to attack it, which may help in the future to reduce the side effects of traditional treatments.
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