2026 Barry Award Supports Exploration of the Inner Workings of a Cancer-Killing Virus

Cathy Miller and Samir Mehanovic of the Department of Veterinary Microbiology and Preventive Medicine in their lab at Iowa State.

Why does a promising cancer‑fighting virus work brilliantly in some patients—yet barely move the needle in others? That question sits at the heart of this year’s Margaret B. Barry Cancer Research Program Award at Iowa State. As clinical studies continue to show encouraging signs for pelareorep, a virus-based therapy now fast-tracked by the Food and Drug Administration (FDA) for cancer treatment trials, one challenge persists: unpredictability. Some patients experience striking responses. Others do not. And scientists still don’t fully understand why.

This year’s Barry Award supports two Iowa State researchers determined to change that: Cathy Miller, professor and chair of Veterinary Microbiology and Preventive Medicine, and Samir Mehanovic, a research scientist III in the same department. Their project seeks to uncover the mystery of pelareorep in a new way—by investigating the internal workings at the molecular level. Their work could ultimately reshape how oncolytic (i.e., cancer-fighting) viruses are engineered for more consistent and potent cancer treatment.

Pelareorep is a naturally occurring mammalian orthoreovirus (MRV) that selectively infects and kills certain cancer cells in the body. Across multiple studies, it has demonstrated a favorable safety profile and the ability to be used in combination with chemotherapy and radiation treatment.

“What this type of virus is actually doing is infecting tumor cells and alerting the immune system that those cells are infected,” said Miller. “The immune system starts to respond and helps the virus kill the tumor. Tumor-associated antigens get released, and the immune system begins targeting similar tumors elsewhere in the body as well.”

This dual action of viral infection plus immune activation helps explain why pelareorep has shown promise in breast, colorectal, pancreatic, and anal cancers. But it also highlights why inconsistent viral replication poses a problem. When replication falters, the chain reaction of immune activation follows suit. These inconsistent results have limited its full therapeutic potential.

The overlooked question: How does a 10‑piece viral genome assemble itself?

Unlike most oncolytic viruses, MRV contains a genome divided into 10 separate double‑stranded RNA segments. For pelareorep to replicate effectively—and for its cancer‑killing action to take hold—all 10 segments must be successfully packaged into each new viral particle as it spreads throughout the body.

Scientists suspect that this intricate assembly process depends on a network of RNA‑RNA interactions, with each segment helping guide the selection of the others. But the exact rules governing this process remain unknown, even after decades of research in viral oncology.

This gap matters. If genome assembly misfires, the virus will become unable to replicate and trigger immune activation, thereby destroying its cancer-killing properties.  

“Right now, we can’t really manipulate the wild‑type virus to make it better because we don’t know what’s needed for each gene segment to be packaged,” Miller said. “We don’t understand how those ten segments find each other to get packaged and replicate. And that’s exactly what we’re trying to figure out.”

Understanding this process could enable the engineering of pelareorep and other multi‑segment oncolytic viruses for greater reliability and therapeutic potency.

Iowa State’s cutting‑edge approach

Using novel RNA interactome-mapping technologies developed in their laboratory, Miller and Mehanovic will investigate the relationships among pelareorep’s genome segments. This process allows them to observe how RNA segments physically and functionally interact inside infected cells, offering a level of resolution not previously available for a virus of this type.

Their goal is to create the first high‑definition map of pelareorep showing exactly how the virus selects, organizes, and packages its genome segments during replication.

“I developed a method where we can take a snapshot of this complex in the infected cells,” Mehanovic said. “We’ve already gotten our first sequencing results back—the method works—and now we can dig deeper.”

Uncovering these answers would represent a great leap forward for oncolytic virotherapy. Rather than modifying delivery systems or immune‑stimulating properties—the typical biomedical engineering focus—the Iowa State team is examining the molecular determinants of viral fitness themselves.

“The Margaret B. Barry Cancer Research Program was established to support exactly this kind of ambitious, foundational cancer research,” explained Peter Dorhout, vice president for research at Iowa State. “This is the sort of high-impact work that requires preliminary data before competing for federal funding.”

Toward next‑generation cancer‑killing viruses

If researchers can decipher how pelareorep orchestrates its segmented genome, they can begin to design next‑generation viruses that replicate more robustly in cancer cells and produce more consistent treatment outcomes.

For Mehanovic, the work is more than scientific curiosity. “Cancer research is very personal to me. My aunt fought breast cancer for years before she died,” he said. “She’s the reason I became a scientist. I don’t want anyone else to go through what she did.”

As Miller and Mehanovic push forward with this next phase of discovery, their shared goal is clear: to deepen our understanding of a uniquely promising virus so that future cancer patients have access to safer, more targeted, and more effective treatment options.

About the Margaret B. Barry Cancer Research Program

Created in 2005 through an estate gift from Margaret Barry, the program supports cancer research by eligible faculty and professional and scientific staff within Iowa State University’s College of Veterinary Medicine. The award provides critical seed funding for innovative ideas, enabling researchers to build collaborations, generate preliminary data, and accelerate breakthroughs that may one day change how cancer is treated.