Cancer Treatment: Genetically Engineered, Sound-Controlled Bacteria To The Rescue

Outside of early detection and chemotherapy in some instances, cancer, of whatever hue, is almost always, a manage-and-see-how-it-ends ailment. Whereas it can be handled effectively when detected early, chemotherapy, as a treatment alternative, presents unpleasant set backs. Besides killing cancers cells, it goes the extra mile of wasting specific surrounding healthy cells, including those in hair follicles, which leads to baldness, and the ones lining the stomach, leading to nausea.

But according to a new new paper published in the journal Nature Communications, researchers appear to have found the right antidote at last. The paper reports that scientists at the California Institute of Technology, Caltech, may have found a better cancer treatment solution in genetically engineered, sound-controlled bacteria that seek and destroy cancer cells.

The publication states that scientists from the lab of Mikhail Shapiro’s lab (a professor of chemical engineering and Howard Hughes Medical Institute investigator) disclosed that they have developed a specialized strain of the bacteria, Escherichia coli (E. coli, for short) which, when injected into a cancer patient’s body, seeks out and infiltrates cancerous tumors. They say once infiltrated, they trigger the bacteria by pulses of ultrasound leading them to produces anti-cancer drugs.

“The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” professor Shapiro says.

According to the publication, the scientists adopted a strain of E. coli called Nissle 1917, already approved for human uses, as the starting point for their work. It adds that after being injected into the bloodstream, these bacteria spread throughout the body where most are destroyed by the patient’s immune system with the exception of the already colonized cancerous tumors, which offer an immunosuppressed environment.

The scientists then transform the bacteria into a useful tool for treating cancer by engineering them to contain two new sets of genes-one for producing nanobodies-therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. These nanobodies allows the immune system to attack the tumor. The other is the genes that trigger the thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.

The publication reports that by inserting the temperature-dependent and nanobody genes, the team effectively created strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42-43 degrees Celsius or 107.6-109.4 degrees Fahrenheit. But because normal human body temperature is less at 37 degrees Celsius or 98.6 degrees Fahrenheit, the bacteria do not immediately start the process of producing their anti-tumor nanobodies when injected into a person. Instead, they quietly grow inside the tumors until they are heated to their trigger temperature by an outside source.

The publication goes on to add that the scientific team was able to heat bacteria in one specific location, potentially deep inside the body where a tumor is growing, using focused ultrasound, an instrument that is similar to the ultrasound used for imaging internal organs, or a fetus growing in the womb. However, the FUS, which is usually focused on a tight point, has higher intensity which causes the tissue in that location, rather than surround tissues, to heat up. And with the ability to control the ultrasound’s intensity, the researchers successfully raised the temperature of the affected tissue to a specific required degree.

Mohamad Abedi, a former PhD student in Shapiro’s group, who co-led the project and is now a postdoctoral fellow at the University of Washington, said: “Focused ultrasound allowed us to activate the therapy specifically inside a tumor.
“This is important because these potent drugs, which are so helpful in tumor treatment, can cause significant side effects in other organs where our bacterial agents may also be present.”

To ascertain that the engineered bacteria strain worked as intended, the team injected bacterial cells into lab mice afflicted with tumors and allowed it time to infiltrate the tumors. Thereafter, they used ultrasound to warm them. After series of trials, they found out that mice treated with this strain of bacteria and ultrasound showed much slower tumor growth than others treated only with ultrasound. But they also found out that some of the tumors in treated mice did not shrink at all.

“This is a very promising result because it shows that we can target the right therapy to the right place at the right time,” Shapiro says. “But as with any new technology there are a few things to optimize, including adding the ability to visualize the bacterial agents with ultrasound before we activate them and targeting the heating stimuli to them more precisely.”

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