Trojan Horse Viruses: Delivering Cancer Treatment Inside Tumors
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Columbia Engineers Build Cancer Therapy That Uses Bacteria and Viruses as a Team
Researchers at Columbia Engineering have built a cancer therapy that makes bacteria and viruses work as a team. In a study published recently in Nature Biomedical Engineering, the Synthetic Biological Systems Lab shows how their system hides a virus inside a tumor-seeking bacterium, smuggles it past the immune system, and unleashes it inside cancerous tumors.
The new platform, called CAPPSID (short for Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery), combines the bacteria’s tendency to find and attack tumors with the virus’s natural preference for infecting and killing cancerous cells. Tal Danino, an associate professor of biomedical engineering at Columbia Engineering, led the team’s effort. Charles M. Rice, an expert in virology at The Rockefeller University, collaborated on the project.”We aimed to enhance bacterial cancer therapy by enabling the bacteria to deliver and activate a therapeutic virus directly inside tumor cells, while engineering safeguards to limit viral spread outside the tumor,” says co-lead author Jonathan Pabón, an MD/PhD candidate at Columbia.
The researchers believe this technology – validated in mice – represents the first example of directly engineered cooperation between bacteria and cancer-targeting viruses.
How it Works: A Trojan Horse for Cancer Treatment
The approach combines the bacteria’s instinct for homing in on tumors with a virus’s knack for infecting and killing cancer cells. “By bridging bacterial engineering with synthetic virology, our goal is to open a path toward multi-organism therapies that can accomplish far more than any single microbe could achieve alone,” says Zakary S. Singer, a co-lead author and former postdoctoral researcher in Tal Danino’s lab.
danino calls this platform “probably our most technically advanced and novel platform to date,” and it’s affiliated with the Herbert Irving Thorough cancer Center at Columbia University Irving Medical Center and Columbia’s Data Science Institute.
Sneaking Past the Immune System
One of the biggest hurdles in oncolytic virus therapy is the body’s own defense system. If a patient has antibodies against the virus – from a prior infection or vaccination – those antibodies can neutralize it before it reaches a tumor. The Columbia team sidestepped this problem by tucking the virus inside tumor-seeking bacteria.”The bacteria act as an invisibility cloak, hiding the virus from circulating antibodies, and ferrying the virus to where it is needed,” Singer explains.
Pabón adds that this strategy is especially crucial for viruses that people are already exposed to in daily 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 says.
Targeting the Tumor
The system’s bacterial half is Salmonella typhimurium, a species that naturally migrates to the low-oxygen, nutrient-rich surroundings inside tumors. Once there, the bacteria invade cancer cells and release the virus directly into the tumor’s interior.
“We programmed the bacteria to act as a Trojan horse, shuttling the viral genome inside the tumor and then lysing themselves to release it,” Singer says.
By exploiting the bacteria’s homing instincts and the virus’s ability to replicate, the researchers created a system that can penetrate and spread throughout the tumor – a challenge for both bacteria-only and virus-only approaches.
Safeguarding Against Runaway Infections
A key concern with any oncolytic virus therapy is controlling its spread. The Columbia team addressed this with a clever molecular trick.
“We engineered the virus so that it can only replicate inside cancer cells,” explains Danino. “This limits its ability to spread to healthy tissues.”
Looking Ahead
This research represents a notable step toward more effective and targeted cancer therapies. The team is now working to refine the system and explore its potential for treating a wider range of cancers.
“This is probably our most technically advanced and novel platform to date,” Danino says. “We’re excited about the possibilities this opens up for the future of cancer treatment.”
Key Takeaways:
Novel Approach: Researchers have combined bacteria and viruses to create a new cancer therapy.
Targeted Delivery: The bacteria act as a delivery system, hiding the virus from the immune system and delivering it directly to the tumor.
Enhanced effectiveness: The combination of bacteria and virus is more effective at killing cancer cells than either approach alone.
Safety Measures: The system is designed to prevent the virus from spreading to healthy tissues.
Future Potential: This technology holds promise for treating a wide range of cancers.
Source: Columbia Engineering. “Engineers build cancer therapy that makes bacteria and viruses work as a team.” ScienceDaily*. ScienceDaily, 18 August 2025.