A Yale researcher developed a vaccine that can slow or halt certain cancers in dogs. And it could be used to treat humans in the future.

By Mallory Locklear march 5, 2024

During a sunny morning on Florida’s Gulf Coast last month, an 11-year-old golden retriever named Hunter bounded through a pine grove. Snatching his favorite toy, a well-chewed tennis ball attached to a short rope, he rolled through the tall grass, with an energy that seemed inexhaustible. A passerby might not have even noticed that this playful golden has only three legs.

For Deana Hudgins, the dog’s owner, it seems almost unthinkable that two years ago Hunter was diagnosed with osteosarcoma, a form of bone cancer that kills upwards of 65% of the dogs it afflicts within 12 months, in his left front leg.

For many years Hunter worked alongside his owner as a search-and-rescue dog, helping find victims of building collapses and other disasters. He no longer performs those duties, but does still help Hudgins train other dogs. The energetic golden can also run, fetch, and catch as well as ever.

And two years since his initial diagnosis, Hunter has no signs of cancer. The dog’s life-saving treatment incorporated typical approaches, including amputation of the left leg and chemotherapy. But Hunter also received a novel therapy — a cancer vaccine developed by Yale’s Mark Mamula.

If we can provide some benefit, some relief — a pain-free life — that is the best outcome that we could ever have.”

The treatment, a form of immunotherapy that is currently under review by the U.S. Department of Agriculture (USDA), which regulates animal treatments, has been subject to multiple clinical trials over the past eight years. And the results are promising; for hundreds of dogs, including Hunter, the vaccine has proved effective.

Mamula, a professor of medicine (rheumatology) at Yale School of Medicine, believes the vaccine offers a badly needed weapon in the fight against canine cancer.

“Dogs, just like humans, get cancer spontaneously; they grow and metastasize and mutate, just like human cancers do,” said Mamula. “My own dog died of an inoperable cancer about 11 years ago. Dogs just like humans suffer greatly from their cancers.

“If we can provide some benefit, some relief — a pain-free life — that is the best outcome that we could ever have.”

Even as recently as a decade ago, Mamula didn’t anticipate that he would one day develop a cancer vaccine for dogs. A rheumatology researcher, he studies autoimmune diseases like lupus and Type 1 diabetes and how the body gives rise to them.

But that work eventually led him to cancer research as well.

Autoimmune diseases, Mamula says, are characterized by the immune system attacking the body’s own tissues; in the case of Type 1 diabetes, the immune system targets cells in the pancreas.

Then several years ago, using what they knew about autoimmunity, Mamula and his research team developed a potential cancer treatment that they say initiates a targeted immune response against tumors.

“In many ways tumors are like the targets of autoimmune diseases,” he said. “Cancer cells are your own tissue and are attacked by the immune system. The difference is we want the immune system to attack a tumor.”

It was a chance meeting with a veterinary oncologist soon thereafter that made Mamula think that this novel treatment might work well in dogs.

Targeting tumors

There are about 90 million dogs, living in 65 million households, in the United States alone. Around one in four dogs will get cancer. Among dogs 10 years or older, that ratio jumps to around one in two.

Yet the therapies used to treat these cancers remain fairly antiquated, Mamula says.

“There have been very few new canine cancer treatments developed in decades — it’s a field that is begging for improvement,” he said.

In 2015, Mamula met a veterinary oncologist named Gerry Post. During his 35-year career Post has treated cancer in snakes, turtles, and zoo animals. But most of his patients are dogs and cats.

Through conversations with Post, Mamula realized that it wouldn’t be difficult to make the leap from human to dog cancers. Together they would launch an early-phase study into Mamula’s dog cancer vaccine.

“Dog and human cancers are quite similar in a number of ways,” said Post, chief medical officer of One Health Company, a canine cancer treatment group, and an adjunct professor of comparative medicine at Yale School of Medicine. “Whether it’s how the cancers appear under the microscope, how the cancers behave, respond to chemotherapy, develop resistance, and metastasize.”

After talking with a veterinary oncologist, Mamula realized that it wouldn’t be difficult to make the leap from addressing human cancers to dog cancers.

Even the types of cancers that afflict dogs and humans are similar. Like humans, dogs can get melanoma, breast cancer, colon cancer, and osteosarcoma, among others.

When it comes to curing these diseases, these similarities bring an important benefit: understanding cancer in one species will help scientists understand cancer in the other. And treatments that work well for one may actually work well for both.

Several types of cancers in both humans and dogs have been found to overexpress proteins known as epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). These include colorectal cancer, breast cancer, and osteosarcoma. One type of treatment currently given to human patients with these cancers involves monoclonal antibodies, proteins that can bind to and affect the function of EGFR and/or HER2. However, patients can develop a resistance to them and their effects wane over time.

For their treatment, Mamula and his team wanted to take a different approach.

Monoclonal antibody treatments are produced from one immune cell and bind to one part of the EGFR/HER2 molecules, but Mamula and his team wanted to induce a polyclonal response.

Doing so, he says, would create antibodies from multiple immune cells, rather than just one, which could bind to multiple parts of the EGFR/HER2 molecules instead of a single area. This would, in theory, reduce the likelihood of developing resistance.

The research team, led by Hester Doyle and Renelle Gee, who are both members of Mamula’s Yale lab, with assistance from the New Haven-based biotechnology company L2 Diagnostics, LLC, tested many different candidates in order to find just the right compound. They eventually found one.

After first testing it in mice, and finding promising results, they initiated their first clinical trial in dogs in 2016.

‘I was willing to try whatever I could’

Deana Hudgins knew there was something special about Hunter before she brought him home as an 8-week-old puppy, back in 2012, and began training him to be her next search-and-rescue partner.

The smallest of 18 puppies from two litters, Hunter wasn’t the obvious choice when she began looking for a partner.

“He was the runt,” said Hudgins, who has been training search-and-rescue dogs since 2001 and now runs her own company, the Center for Forensic Training and Education, which provides canine training in Ohio and Florida. “But in his case, it made him a little scrappy. He was small but very confident and very brave.

“When all of the other puppies were sleeping at the end of the day, he was still running around, climbing all of the toys, retrieving things. We need confident puppies, and that’s what he possessed.”

By the time he was a year old, Hunter began aiding searches at sites across the United States, working with local law enforcement and the Federal Emergency Management Agency (FEMA), following natural disasters. His first search, in 2014, was at the site of a mudslide in Oso, Washington that killed 43 people. In his final FEMA search, he helped search for victims of the devastating condominium collapse in the Miami suburb of Surfside, Florida, in June 2021. Hunter was involved in hundreds of searches in the years between.

In 2022, Hunter was still very active — and had just earned another service certification — when Hudgins noticed that he seemed uncharacteristically sore following a five-day training class.

“I’ve always been very proactive with my dogs because I spend every day with them, and so I notice very little things,” she said. “And he’s not a dog to limp.”

A veterinarian assumed that Hunter had strained something, suggesting anti-inflammatories, but Hudgins insisted on an x-ray. The test revealed the osteosarcoma in Hunter’s leg.

After doing a lot of research, and consulting with different veterinary groups about what steps to take, Hudgins decided that amputation offered the best chance for Hunter’s survival, along with chemotherapy.

But during that research, Hudgins had also come across Mamula’s vaccine trial. So she reached out to a colleague, James Hatch, a former Navy SEAL who trained dogs in the military and whose nonprofit supports service dogs. Hudgins knew that Hatch also happened to be at Yale, where he is a student in the Eli Whitney Students Program.

“I was willing to try whatever I could to keep [Hunter] around as long as possible,” said Hudgins. “We ask a lot of our working dogs. They work in environments that are very dangerous and often deadly. And my promise to all of them is I will do whatever I have to do to give them the best, healthiest, longest life possible. Dogs don’t survive this disease so there was no downside to me for trying the vaccine.”

Hatch connected her with Mamula, and soon Hunter was part of the clinical trial. He received his first vaccine dose ahead of his amputation surgery, his second before initiating chemotherapy, and a booster last summer.

Twenty-two months since his cancer diagnosis, Hunter is now considered a long-term osteosarcoma survivor and Hudgins says he’s thriving.

“He adjusted very well to his front limb amputation,” she said. “He continues to run around the yard. He swims in the pool. He comes with me to training and chases the other dogs around the yard.”

During a recent morning in Florida, Hunter drifted toward a nearby pond while playing outside. Hudgins, knowing the potential risks of straying too close to a pond in Florida (“There are alligators everywhere.”), quickly called him back. Hunter immediately returned to her.

“From a very young age, Hunter wanted to learn the rules of the game,” she said. “He was eager to go to work every day. I am very, very lucky to have been able to be his partner for 10 years. Hunter is one of those once-in-a-lifetime dogs.”

‘A whole new toolbox’

Hunter’s positive response to the treatment is one many other dogs have experienced as well.

To date, more than 300 dogs have been treated with the vaccine during a series of clinical trials, which are still ongoing at 10 sites in the U.S. and Canada. The findings, which have been published in a peer-reviewed study, have shown that the treatment creates antibodies that are able to home in on and bind to tumors, and then interfere with the signaling pathways responsible for tumor growth.

According to the research team, the vaccine increases the 12-month survival rates of dogs with certain cancers from about 35% to 60%. For many of the dogs, the treatment also shrinks tumors.

While future studies will determine if the vaccine can reduce the incidence of cancer in healthy dogs, the treatment for now remains a therapeutic treatment option after a cancer diagnosis has been made.

Witnessing the happiness that successful therapies provide to families with dogs is incredibly rewarding.

But even this represents something more than just “a new tool” in the fight against canine cancer, Post says. It’s a whole new toolbox.

“And in veterinary oncology, our toolbox is much smaller than that of human oncology,” he said. “This vaccine is truly revolutionary. I couldn’t be more excited to be a veterinary oncologist.”

Mamula has created a company, called TheraJan, which aims to eventually produce the vaccine. Last year, the company (whose name is inspired, in part, by the late Yale immunologist Charles Janeway, who was Mamula’s mentor) won a Faculty Innovation Award from Yale Ventures, a university initiative that supports innovation and entrepreneurship on campus and beyond.

While launching clinical tests of the vaccine’s effectiveness in humans may be a logical future step, for now Mamula is focused on getting USDA approval of the vaccine for dogs and distributed for wider use.

No matter where it goes, it’s a project close to his heart.

“I get many emails from grateful dog owners who had been told that their pets had weeks or months to live but who are now two or three years past their cancer diagnosis,” he said. “It’s a program that’s not only valuable to me as a dog lover. Witnessing the happiness that successful therapies provide to families with dogs is incredibly rewarding.”

And once the vaccine becomes available for public use, he says, for working dogs like Hunter it will always be free of charge.

 media contact Fred Mamoun: fred.mamoun@yale.edu, 203-436-2643

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