Hugo is, in the words of his owner Wendy Legge, a “gentle giant”—a 65-pound mixed-breed dog who defers even to the family’s two cats, Hudson and Rosie. He has spent 13 years with the Legge family in a household that cherishes its geriatric animals.

But earlier this year, a routine dental cleaning delivered a devastating surprise: a nodule in his mouth tested positive for malignant melanoma.

Oral malignant melanoma is one of the most common tumors in dogs and is notoriously aggressive, spreading quickly and often proving resistant to chemotherapy. The prognosis is frequently poor, forcing owners to weigh aggressive, costly treatments against their dog’s quality of life.

“He’s not a young dog, so we didn't know what to expect,” Wendy Legge says. For the family, the diagnosis launched them on a swift and challenging journey to find the best possible option for their beloved companion.

The search for a systemic solution

After a rapid initial referral to the University of Minnesota (UMN) Veterinary Medical Center (VMC), the Legges learned that Hugo’s best chance required surgery, followed by radiation therapy to clean up residual cells after the tumor margins didn't come back clean.

But for aggressive cancers like melanoma, local treatment—surgery or radiation—isn't enough. Cancer cells often circulate, ready to metastasize (spread) to other organs, such as the lungs. Since existing chemotherapy options are ineffective, researchers need a systemic solution to "mop up" these hidden cancer cells.

That's where the VMC Medical Oncology Service and the Veterinary Clinical Investigation Center (CIC) stepped in, offering a new path: a Phase II clinical trial testing a novel cancer vaccine.

The trial is a highly collaborative effort, led by Antonella Borgatti, medical oncologist at the College of Veterinary Medicine, and George Aslanidi, a viral vector and vaccine expert at the UMN Hormel Institute. With potential implications for both animal and human patients, it’s the kind of project that leverages the unique integration of UMN's veterinary and translational research experts to rapidly translate advanced scientific discovery from the lab bench to the clinic.

Exposing the invisible

The vaccine uses a concept at the forefront of human and veterinary gene therapy: a modified adeno-associated virus (AAV) vector.

“One of the biggest challenges in cancer treatment is immune evasion,” Borgatti says. “Cancer cells develop ways to hide from the body’s immune system, specifically the T cells that are supposed to attack and destroy them.”

The AAV vaccine is engineered to overcome this evasion. It acts like a tiny, specialized delivery truck, transporting the genetic blueprints of three specific melanoma antigens (the targets) directly into immune cells.

“This process essentially trains the dog’s immune system,” Aslanidi says. “We are trying to make the hidden cancer cells more recognizable so they can be better targeted and attacked by the T cells. The long-term hope is that this boosts the immune system to patrol the body and stop the spread of metastasis.”

An earlier pilot study for this vaccine has already established a critical first step: safety. “What we learned so far is that the vaccine is well tolerated,” Borgatti says. The team recently submitted results from that study for publication.

And while this investigational AAV vaccine is a novel application, the foundation is proven. Aslanidi notes that AAV vectors are already the basis for several FDA-approved drugs in humans for genetic diseases such as muscular dystrophy and hemophilia. And like the melanoma vaccine, many of these saw their first trials in dogs.

A dedication to comparative medicine

The researchers emphasize that companion dogs are the ideal model for this work. Unlike laboratory animals, dogs develop naturally occurring cancers in the same environment as humans, and because they are living longer, they suffer from similar age-related diseases.

For owners Wendy and her husband Gordon, the decision to enroll Hugo was straightforward. 

“We believe in research,” she noted. “If Hugo could help with the research while being treated, why not?”

Their willingness to participate is essential to the study, which recently received a significant five-year grant from the National Institutes of Health to expand its scope, proving the high scientific interest in the comparative model.

It’s a model that both accelerates scientific advancement and offers mutual benefits to humans and animals. “This study may pave the way to new possibilities in treating human cancers,” Alsandi notes, “but it’s also such an interesting opportunity for veterinary practice, in getting access to these very expensive drugs that companion animals aren’t typically able to get.”

A new lease on life

Participation meant a screening, a CT scan, surgery, radiation, and the vaccine dose, followed by a series of monitoring appointments to assess Hugo’s health and collect blood samples to measure his immune response.

Months later, Hugo is thriving. “His six-month check is at the end of October. He’s bounced back. There’s zero difference—he's completely his normal self,” Wendy Legge says. “It’s amazing for his age.”

While there are no guarantees about what’s to come for Hugo, his quality of life remains excellent, demonstrating the profound potential of this therapeutic vaccine approach when combined with standard care. By enrolling in the trial, Hugo and the Legge family are providing the crucial data that could slow down the process of metastasis in countless dogs—and potentially, humans—in the future.