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Scientists explore fighting cancer with sound-controlled bacteria

The tests on mice showed promise that the treatment could one day be an alternative to chemotherapy.

(CN) — Scientists at the California Institute of Technology are using genetically engineered bacteria and ultrasound to treat cancerous tumors.

According to research published this week in the journal Nature Communications, researchers in the lab of chemical engineering professor Mikhail Shapiro have engineered a specialized strain of the E. coli bacteria that infiltrates tumors. Using focused ultrasound, the bacteria can then be activated to release anti-cancer drugs. The researchers successfully used the treatment to slow tumor growth in mice.

Mohamad Abedi, a co-author of the research and post-doctoral fellow at the University of Washington, explained that tumors are adept at suppressing the immune system’s attacks on the tumor. The researchers took advantage of that immunosuppressive environment as a way for the genetically engineered bacteria to enter the tumor without getting destroyed by the immune system.

“If you have microbes introduced into a patient, that immune system will get rid of all of it, except where there is a tumor. There, these microbes will stay alive and propagate in the tumor,” said Abedi.

When activated by the focused ultrasound, the bacteria can battle the cancer cells from inside the tumor. This could potentially lessen the effects of the cancer treatment on healthy cells like the hair follicles or stomach lining, which can be wiped out during chemotherapy treatment, resulting in baldness and nausea.

Abedi said the genetic engineering proved crucial to the treatment. The bacteria had to be recalibrated to treat the cancer with a targeted approach rather than systemically, meaning the researchers needed the ability to prompt the bacteria’s release of the tumor-suppressing nanobodies only when and where directed.

Ultrasound, typically used for imaging internal organs or seeing a fetus during pregnancy, can be used in a higher intensity in a small area to heat up the location. The scientists identified heating through focused ultrasound as an effective means of directly targeting the bacteria within the tumor. All they needed was a way to make the bacteria respond to the change in temperature.

“Nothing will happen unless you’re going to have an antenna that sees it and says, ‘Okay, I see the signal and now I’m going to activate the program,’” Abedi said.

The researchers turned to nature to search for bacteria that already had some form of built-in temperature sensor. Abedi pointed to salmonella as a microbe that often infects humans and has this temperature sensor. With this, they could begin engineering the bacteria.

“We took out the genetic code for that sensor and modified it slightly to turn on at the temperature we want,” said Abedi. “And then that was our antenna. We looked in nature and nature already solved this problem. We had to do some engineering, but at the end we had the sensor and then together with the ultrasound, you can have this system where you send a signal, and the bacteria would now understand it.”

The researchers engineered the bacteria to release the tumor-suppressing nanobodies upon reaching nearly 108 degrees, outside the range of a typical high fever. This prevents the bacteria from producing and releasing the anti-tumor nanobodies right when they are injected into the body, Instead, they must wait until they are heated up by the focused ultrasound.

Though Abedi cautioned that there is a long way to go before the treatment begins trials outside of mice, he noted that the treatment is “conceptually feasible at this point” and could prove to be an exciting new cell-based cancer therapy.

Abedi said other therapies that engineer a patient’s own immune cells to better fight tumors are “rapidly advancing.” However, he noted that these therapies are limited by their high costs and the ability of even the smallest tumors to fend off the immune system.

“The exciting thing about microbial therapy is you do not need to extract cells from the patient, so that makes it much cheaper and much more generalizable,” said Abedi. “Microbial therapy could have very good implications in terms of making these kinds of therapies more accessible because the technology doesn’t need a lot of expensive work beforehand.”

Abedi suggested that future research could investigate “symbiotic therapy” where the patient’s engineered immune cells attack the tumor from the outside and the engineered bacteria work in conjunction from inside the tumor.

“The immune cells are very good at being trained at killing the tumor and the microbial cells are very good at getting into areas that the trained immune cells cannot go to,” Abedi said. “They can work together to accomplish the goal.”

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