Artist’s representation of a bacterial cell. Credit: Centers for Disease Control and Prevention/James Archer
Since its inception, chemotherapy has proven to be a valuable tool in the treatment of many types of cancers, but it has one significant drawback. In addition to killing cancer cells, it can also destroy healthy cells like those in the hair follicles, causing baldness, and those lining the stomach, causing nausea.
Now, scientists at the California Institute of Technology (Caltech) may have a better solution: genetically engineered, sound-controlled bacteria that seek out and destroy cancer cells. In a new article published in the journal
To transform the bacteria into a useful tool for treating cancer, the research team engineered them to contain two new sets of genes. One set of genes is for producing nanobodies, which are therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. The presence of these nanobodies allows the immune system to attack the tumor. The other set of genes act like a thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.
By inserting the temperature-dependent and nanobody genes, the team was able to create strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42-43 degrees
“Focused ultrasound allowed us to activate the therapy specifically inside a tumor,” says Mohamad Abedi (PhD ’21), a former PhD student in Shapiro’s group who co-led the project and is now a postdoctoral fellow at the
“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.”
Reference: “Ultrasound-controllable engineered bacteria for cancer immunotherapy” by Mohamad H. Abedi, Michael S. Yao, David R. Mittelstein, Avinoam Bar-Zion, Margaret B. Swift, Audrey Lee-Gosselin, Pierina Barturen-Larrea, Marjorie T. Buss and Mikhail G. Shapiro, 24 March 2022, Nature Communications.
Funding for the research was provided by the Sontag Foundation, the Army Institute for Collaborative Biotechnologies, and the Defense Advanced Research Projects Agency.
The researchers’ paper, “Ultrasound-controllable engineered bacteria for cancer immunotherapy,” appears in the March 24 issue of Nature Communications. Shapiro’s and Abedi’s co-authors include Michael S. Yao (BS ’21), formerly of Caltech and now at the University of Pennsylvania, who is co-lead author; David R. Mittelstein (MS ’16, PhD ’20), formerly of Caltech and now at UC San Diego; Avinoam Bar Zion, visitor in chemical engineering at Caltech; Margaret B. Swift of the Howard Hughes Medical Institute; Audrey Lee-Gosselin, formerly of Caltech and now at the Indiana University School of Medicine; Pierina Barturen-Larrea, research technician in Caltech’s Division of Chemistry and Chemical Engineering; and Marjorie T. Buss, graduate student in chemical engineering.