Bacterial “Trojan Horse” Delivers Cancer-Killing Virus to Tumors
Researchers paired bacteria and viruses in a novel system to target tumors and trigger powerful immune responses.
Combining viruses and bacteria may sound like a bad idea, but it could form a new approach to cancer treatment.
Researchers have designed non-toxic bacteria that can deliver cancer-killing viruses to tumors, demonstrating a new way to fight cancer.
Oncolytic viruses are a promising cancer treatment strategy
Oncolytic viruses selectively infect, replicate within, and destroy tumor cells, while leaving healthy cells intact. By inducing immunogenic cell death, they also trigger antitumor immune responses.
They represent a promising strategy but have limited efficacy against solid internal tumors as they are detected and cleared by the immune system before they reach the tumor. Oncolytic viruses are generally delivered directly to the tumor, which can be invasive and, in some cases, dangerous.
By containing an oncolytic virus within a bacterial vector, the authors of the new work hoped to deliver it directly to the tumor, non-invasively.
“I was already being a little bit crazy asking, ‘How can I use a live organism to help treat disease?’” said Prof. Neil Forbes, corresponding author of the paper. “Now, the question is: How can I use two organisms to treat a disease, but I’m going to have one organism control the other organism that’s now going to treat the cancer?”
How the virus-carrying bacteria system works
Non-pathogenic, therapeutic Salmonella has been shown to preferentially colonize tumors over healthy tissue, can invade epithelial cells, and can sense the intracellular environment.
Making use of these properties, Forbes and his team created a virus-delivering Salmonella vector (VDS) that invades tumor cells and releases a plasmid containing the genome of an H-1 parvovirus, an oncolytic virus. The Salmonella vector was engineered to protect the parvovirus genome.
H-1 parvovirus
H-1 parvovirus is a small, single-stranded (ss) DNA virus. It is naturally oncolytic and nonpathogenic in humans. Its selectivity for cancer cells is based on its high dependence on cellular factors involved in proliferation and differentiation that are dysregulated in tumor cells.
The viral genome was transported to the tumor cells’ nuclei, where it was translated into non-structural and capsid proteins. As the functional virions assembled from these proteins, the tumor cells lysed and released the virus particles, enabling them to infect more cancer cells in the local environment.
As the parvoviruses induced lytic cell death, immune cells were recruited to the tumor and initiated antitumor immunity.
Treating liver and pancreatic cancers
Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are the third- and fourth-leading causes of cancer deaths, with few treatment options available and poor prognoses.
H-1 parvovirus has demonstrated efficacy against hepatoma cells with null or mutated p53 and PDAC cells expressing SMAD4, leading the researchers to hypothesize that the VDS/parvovirus system may be effective against HCC and PDAC.
In murine tumor models of HCC and PDAC, VDS/parvovirus reduced tumor volume and increased overall survival, activating innate and adaptive immune responses and converting the tumor microenvironment from immunosuppressive to immunostimulatory.
“Those immune responses are really important, because they’re the ones that tumors shut off so that your immune system doesn’t clear the tumor itself,” explained Forbes. “Tumors have to evolve with time in order to shut those systems off, so we’re turning them back on by putting pathogens into the tumor.”
The immune responses to the VDS/parvovirus treatment also trained the immune system to recognize and respond to future tumors, indicating that it may prevent metastasis and recurrence.
There were no major differences in the effects of the VDS/parvovirus therapy when it was administered by intravenous injection versus being injected directly into the tumor.
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“Injecting treatments directly into internal tumors is incredibly difficult and often dangerously invasive for cancer patients,” said Shradha Khanduja, first author of the paper. “This therapy completely bypasses that hurdle by utilizing a simple, standard intravenous line, allowing the engineered bacteria to safely navigate through the bloodstream and hunt down deep-seated tumors on their own.”
Towards a new cancer therapy
“Our goal is to build therapies that don’t just shrink tumors, but give patients real, lasting time,” said Khanduja. “Seeing these results in two of the deadliest cancers tells us we’re on the right path and that biology still has tools we haven’t fully tapped.”
The VDS system forms a platform for the researchers to investigate whether different virus types, including double-stranded (ds) DNA, dsRNA, ssRNA, and ssDNA viruses, could also hold promise for cancer therapy.
While the researchers confirmed that the VDS/parvovirus therapy was safe, further research is needed to assess off-target viral delivery and replication.
The in vivo experiments were also performed in subcutaneous tumor models, which do not fully capture the complex immune and architectural states of naturally forming tumors.
“There’s so much more research to be done before this treatment could be available to humans, but the potential of giving years to a liver or pancreatic cancer patient is exciting,” said Forbes.
Reference: Khanduja S, Raman V, Hall CL, Howell LM, Dessel NV, Forbes NS. Salmonella vector creates de novo parvovirus that reduces solid tumors and forms antitumor immune memory. Cell Rep Med. 2026. doi: 10.1016/j.xcrm.2026.102839
This article is a rework of a press release issued by The University of Massachusetts. Material has been edited for length and content.
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