Healthcare (Commonwealth Union) – Scientists at Columbia Engineering have created a new cancer treatment that makes bacteria and viruses work together. In a paper released today in Nature Biomedical Engineering, the Synthetic Biological Systems Lab explains how their method tucks a virus inside a bacterium that naturally homes in on tumors, allowing it to bypass the immune system and release its payload once inside cancerous tissue.
This approach combines the bacteria’s natural drive to locate and invade tumors with the virus’s ability to infect and destroy cancer cells. The project, named CAPPSID (short for Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery), was led by Tal Danino, associate professor of biomedical engineering at Columbia. He collaborated with Charles M. Rice, a virology specialist at The Rockefeller University.
“Our goal was to improve bacterial cancer therapy by equipping bacteria to transport and trigger a therapeutic virus directly in tumor cells, while also building in safeguards to prevent the virus from spreading outside the tumor,” explains co-lead author Jonathan Pabón, an MD/PhD student at Columbia.
The team suggests that this innovation — successfully tested in mice — marks the first time bacteria and cancer-targeting viruses have been intentionally engineered to work in tandem.
The strategy merges the bacteria’s natural ability to target tumors with the virus’s talent for invading and destroying cancer cells.
Zakary S. Singer, co-lead author and former postdoctoral researcher in Tal Danino’s lab indicated that by bringing together bacterial engineering and synthetic virology, we aim to create multi-organism treatments capable of achieving outcomes no single microbe could manage on its own.
Danino, who is also connected with the Herbert Irving Comprehensive Cancer Center at Columbia University Irving Medical Center and Columbia’s Data Science Institute stated that this is likely their most innovative and technically advanced platform so far.
A major challenge in oncolytic virus therapy is the patient’s immune defenses. If the body has existing antibodies against the virus — due to past infections or vaccinations — they can eliminate it before it reaches the tumor. To overcome this obstacle, the Columbia researchers concealed the virus inside tumor-homing bacteria.
Singer noted that the bacteria function just like a shield, masking the virus from antibodies in circulation and delivering it directly to the tumor.
Pabón emphasizes that this method is particularly valuable for viruses that people commonly encounter in everyday life.
“Our system demonstrates that bacteria can potentially be used to launch an oncolytic virus to treat solid tumors in patients who have developed immunity to these viruses,” he explained.
The bacterial component of the system is Salmonella typhimurium, a species that naturally moves toward the oxygen-poor, nutrient-rich environment found inside tumors. Once inside, the bacteria infiltrate cancer cells and release the virus directly within the tumor.
Singer pointed out that they engineered the bacteria to act like a Trojan horse, carrying viral RNA into tumors and then breaking open inside the cancer cells to release the viral genome, which can then spread from one cancer cell to another.
By combining the bacteria’s innate tumor-targeting behavior with the virus’s capacity to replicate inside cancer cells, the researchers developed a delivery mechanism capable of penetrating the tumor and dispersing throughout it—a challenge that has hindered therapies using only bacteria or viruses.
A major concern for any therapy involving live viruses is preventing them from spreading beyond the tumor. The team addressed this with a molecular safeguard: the virus is unable to propagate without a specific molecule supplied exclusively by the bacteria. Since the bacteria remain confined to the tumor, this essential factor (a protease) is absent elsewhere in the body.
