Escherichia coli (E. coli) is a bacterium that often appears in prime-time news due to food poisoning outbreaks. Apart from relatively benign symptoms like stomach cramps and diarrhea, certain strains can cause serious kidney damage or even death. Globally, around half a million deaths are attributed to E. coli infections.
While most folks are aware of the potential danger posed by this bacterium, very few are aware of its “good” side. The vast majority of E. coli strains are actually relatively benign. Quite a few are actually an integral part of a healthy human digestive system.
These probiotic bacterial strains are of high interest in cancer research. Since they have evolved to co-exist with the human immune system, they offer us a chance to target cancer cells and tumors in non-invasive ways.
In a recent study published in Nature, researchers at Columbia University reported some success in using genetically modified strains of probiotic E. coli to create a vaccine that targeted tumors in mice. We could be on the cusp of a future where highly personalized cancer vaccines can treat even advanced tumors.
Why Use Bacteria for Cancer Treatment?
Using bacterial immunotherapy against cancer is nothing new. In the 1890s, William B. Coley, a brilliant physician at the New York Hospital, noticed that a bacterial infection often caused certain types of cancers to disappear.
The disease was erysipelas, a common skin infection caused by Streptococcus bacteria. Coley tried to replicate this effect by injecting bone cancer patients with the bacteria, and eventually developed a cocktail of bacterial toxins that became known as Coley’s Toxin.
Although he found some success in these treatments, lack of consistency in results, combined with the rise of more effective treatments like radiation caused a general lack of interest in Coley’s immunotherapy approach for several decades.
Since the 1950s, several other breakthroughs have shown us that Coley’s approach was sound and effective. Perhaps the best example of these is the BCG Vaccine – originally given to newborn children to protect against Tuberculosis, the vaccine was discovered to have potent effect against bladder cancer.
In the last few decades, advances in microbiology and genetics have increased scientific interest in using bacteria to kill tumor cells. Several different approaches are being explored right now:
- Use the bacteria to stimulate/train the human immune system to attack cancer cells
- Genetically engineer the bacteria to deliver toxins or drugs directly inside tumors
- Programming bacteria to colonize tumors and deprive it of oxygen, nutrients etc.
The Columbia study involved the first approach, using a probiotic form of E. coli to help the body’s immune system identify cancer cells with greater efficiency. The specific strain used in the study also boasts a long and interesting history.
The Story of E. coli Nissle 1917
The First World War involved long and brutal battles of attrition in highly unsanitary trenches. Tuberculosis, typhus, and dysentery were widespread on both sides. However, in the German trenches, Dr. Alfred Nissle spotted an anomaly – a lone soldier who was left untouched by dysentery or any stomach issues.
A closer look at his stool sample revealed the presence of a strange strain of E. coli that was helping the soldier fight off stomach infections caused by the Shigella bacteria. The new strain was named E. coli Nissle 1917 in honor of its discoverer.
Subsequent research in the last 100 years has shown us that while the dangerous strains of E. coli destroy the stomach linings, the Nissle strain has the opposite effect. It can actually inhibit the growth of other harmful bacteria and has been used to develop multiple probiotic medications.
In recent years, multiple immunotherapy studies have focused on E. coli Nissle 1917. As explained here by Gerald Vockley, MD, genetically engineered Nissle strains have shown promise in treating Phenylketonuria, a rare and debilitating genetic disorder that affects the entire body.
For cancer treatments in particular, there are several reasons why this particular strain is a popular choice:
- Natural Probiotic: unlike other E. coli strains, Nissle 1917 does not cause any diseases or toxicity in the body, and can be safely cleared from tissues without any systemic effects
- Tumor Targeting: this strain has the ability to thrive in a hypoxic environment, like the one found inside cancer tumors
- Immune Stimulation: it has the inherent ability to coexist alongside the immune system while still stimulating an immune response
- Easily Modifiable: the genetic structures of the E. coli strains have been fully sequenced and mapped, making it ideal for precise genetic modifications
The Implications of the Columbia University Study
The mutations responsible for creating cancer cells often release abnormal proteins called “neoantigens.” Since they are not present in healthy cells, the body’s immune system can attack them and destroy the cancer cells as a natural response.
However, many cancers evade this by suppressing the immune cell activation, or other similar means. To counter this, the Columbia team genetically engineered the E. coli Nissle 1917 to carry neoantigens and deliver them to tumors.
They also added features that help the bacteria overcome any immunosuppressive action by the tumor cells. The net result is a massive boost to the immune system, allowing it to effectively target the tumor cells without damaging healthy tissues.
In humans, the vaccine has several potential benefits. It can be programmed to carry specific neoantigens, which can vary from cancer to cancer and in each individual patient, resulting in highly efficient and customized treatment protocols.
Apart from killing advanced tumor cells, the vaccine also helped prevent the progression of early-stage cancers in the lab mice. This could offer us new ways to create human vaccines that prevent the recurrence of cancer in patients who have gone into remission, as explained by the Mayo Clinic.
