Researchers aim to fight aggressive cancer with a virus

Hear the word “virus” and dreadful thoughts of deadly diseases often come to mind. But what if a virus could be used for healing instead? 

Scientists at Virginia Tech are engineering viruses to carry a cancer-killing molecule directly to brain tumors — a novel approach to treating glioblastoma, one of the most aggressive and treatment-resistant cancers. 

The National Institutes of Health-funded study is being led by Samy Lamouille, assistant professor at the Fralin Biomedical Research Institute at VTC, and James Weger-Lucarelli, associate professor in viral genetics and host interactions at the Virginia-Maryland College of Veterinary Medicine. 

The treatment combines two cutting-edge strategies: using naturally brain-seeking viruses as delivery vehicles and training these viruses through directed evolution to become even more effective at targeting cancer cells while sparing healthy tissue. 

Deadly cancer 

Glioblastoma patients face a grim prognosis even with aggressive treatment that includes surgical removal of the tumor followed by radiation and chemotherapy. This intensive approach only extends the typical patient's life 12 to 15 months, highlighting the urgent need for more effective therapies. 

"It's a very complex disease with significant heterogeneity," said Lamouille. "There are many variations of this disease from one patient to another." 

The difficulty in treating glioblastoma stems from several factors. The tumors are highly invasive, making complete surgical removal nearly impossible. Cancer cells left behind after surgery often include glioblastoma stem cells, particularly resilient to both chemotherapy and radiation.  

"Some of these cells can become dormant, they stop dividing but remain alive," said Lamouille. "That makes them hard to target, because chemotherapy and radiotherapy are designed to kill cells that are actively dividing."

When these cells reactivate, the tumor returns, often in a different location in the brain. 

A new way to combat glioblastoma

The key to the new approach is a peptide called JM2, which Lamouille discovered can kill these resistant glioblastoma stem cells.  

While studying how cancer cells communicate with each other and their surrounding environment, he noticed that a protein called connexin43 had an unusual location inside glioblastoma stem cells.  

Instead of sitting at the cell surface where it normally facilitates communication between cells, the protein was inside the cells, interacting with microtubules — structures essential for cell division and migration. 

To target this interaction, Lamouille used a peptide originally developed by his colleague Robert Gourdie, a professor at the Fralin Biomedical Research Institute. When tested on glioblastoma stem cells, the results were striking. 

"While these cells were not killed by chemotherapy, the peptide had a strong effect across all the glioblastoma stem cells we tested from different patients," Lamouille said.

Peptides, however, break down quickly in the bloodstream and cannot easily cross the blood-brain barrier, the protective shield that prevents most substances from entering brain tissue.  

"Even when a treatment works in the lab, getting it to the brain is a major challenge," said Lamouille.

Conversation leads to collaboration

The solution emerged from a conversation between Lamouille and Weger-Lucarelli at a cancer research meeting at the Fralin Biomedical Research Institute. 

“My mom, Leila, passed away from lung cancer, and I've always wanted to help prevent that from happening to other people, which is why I was at the cancer conference,” Weger-Lucarelli said. “So this project represents a significant shift in research direction for me.” 

Weger-Lucarelli is a virologist who works with alphaviruses. 

“The virus has a natural property — it's able to get across the blood-brain barrier and get into the brain when it's delivered through the bloodstream," Weger-Lucarelli said. "So that’s the origin of those conversations."  

Oncolytic viruses — viruses that preferentially attack cancer cells — have been studied as potential cancer treatments for over a century. In the 1950s, doctors noticed that some cancer patients experienced tumor regression after viral infections, sparking research into viral therapies.  

That work was largely abandoned when chemotherapy drugs emerged, but interest has resurged in recent years as many cancers, including glioblastoma, have proven resistant to conventional treatments. 

“We can modify the viruses to produce these proteins, peptides that have therapeutic purposes, like JM-2,” Weger-Lucarelli said.   

To make the viruses even more effective, the researchers are using directed evolution — a technique that harnesses the virus's natural ability to evolve quickly. 

“We can use the power of the fact that the virus evolves quickly to select for viruses that have desirable properties,” Weger-Lucarelli explained, comparing the process to how wolves were selectively bred over thousands of years to become different dog breeds. In this case, the researchers are selecting for viruses that more precisely target cancer cells while leaving healthy tissue alone.  

Hope for dogs and people 

In the long term, the team is planning to test the treatment in clinical trials with dogs — a step that could accelerate the path to human clinical trials while potentially offering new treatment options for canine patients.  

The researchers are currently in the preclinical phase, testing the engineered viruses in mouse models to confirm they deliver the peptide effectively, kill cancer stem cells, and reduce tumor size.   

Success in these studies could lead to regulatory approval processes and eventually human clinical trials, though Lamouille acknowledges the journey is long.  

"From the initial discovery to a phase three clinical trial, it would take more than 10 years," he said.

Despite the lengthy timeline, the potential to improve outcomes drives the work forward. "The real success," Lamouille said, "would be seeing this become a treatment for glioblastoma patients."

Co-investigators include:

• Robert Gourdie, the Heywood Fralin Professor at the Fralin Biomedical Research Institute and director of the institute’s Center for Heart and Reparative Medicine Research
• John Rossmeisl, the Dr. and Mrs. Dorsey Taylor Mahin Professor of Neurology and Neurosurgery and associate head of Small Animal Clinical Sciences in the veterinary college
• Maosen Wang, research assistant professor and pre-clinical small bore imaging core manager at the institute
• Sheryl Coutermarsh-Ott, associate clinical professor in the Department of Biomedical Sciences and Pathobiology at the veterinary college