Mark Mamula has combined his love of dogs and his work in immunology to create a lifesaving immunotherapy for canine cancer.
It could help humans at some point, but Mamula, a professor of rheumatology at the Yale School of Medicine, is happy to be saving the lives of dogs.
“Mark is all for the dogs. That’s his main goal,” said Rick Kneisel of Wilmington, Ohio, whose golden retriever Ranger was given an additional 3½ years of life after Mamula’s treatment shrank Ranger’s osteosarcoma tumor to nothing.
Mamula now has a patent and has launched a company, TheraJan LLC, with rented lab space in New Haven, financed by dog-loving investors, that he hopes soon will enable every veterinarian to be able to administer his “therapeutic vaccine” to dogs with osteosarcoma and other cancers. He’s awaiting licensing from the U.S. Department of Agriculture, he hopes in about six months.
There are fewer than 350 veterinary oncologists in the United States, Mamula said.
“It’s difficult to get your dog with cancer into a specialist that knows dog cancers perfectly,” he said. “So most people obviously take their dogs to their local vets. … The local vet, if they’re skilled, can potentially provide chemotherapies or other therapies, and they could also provide our therapy.”
Mamula’s lab at Yale has studied immune system diseases like lupus and type 1 diabetes for 30 years, he said.
“I’m actually an immunologist by training and so-called immunotherapies have really changed the landscape of cancer care in humans, certainly in the last probably four or five years,” Mamula said.
“Our interest in dog cancers arose a bit by serendipity,” he said. A dog lover, whose yellow Labrador retriever, Savannah, had died of cancer, Mamula met a veterinary oncologist at a party and started talking about using dogs as a model for immunotherapies, rather than mice.
“Dogs, just like humans, get spontaneous cancers. They arise naturally,” he said. “They get virtually all of the same cancers that humans do, such as breast cancer. They get melanoma, colon cancer, osteosarcoma, lung cancer, pancreatic cancer, all of these things, and they almost all have identical growth and mutations that human cancers have.”
Also, treatment of canine cancers is similar to human cancers: CT scans, radiation, chemotherapy and surgery.
Mamula suggested to the veterinary oncologist that they start a clinical trial, which they did, in Norwalk. That site now is closed, but there are now 11 sites across the country and in Canada. The closest to Connecticut is in Manassas, Va.
Information on the trials can be found at therajan.com or the Canine Cancer Alliance, www.ccralliance.org. The vaccine is provided for free. Other costs, such as imaging, must be borne by the dog owner.
“We published the early results of those studies, and they’re compelling,” Mamula said. “And just by way of background, generically to emphasize the importance of studying and treating dog cancers, there are about 65 million households in the country that have a dog or more than one dog. There are about 90 million dogs in the United States alone.”
Mamula said about one in four of those dogs will get cancer.
“If your dog happens to live to 10 years old, then about one in two dogs will get cancer,” he said. “So you can appreciate the numbers out there. Of course, people are very connected to their dogs, as we are.”
Mamula now has two golden retrievers, Tripp, 11, and Sherman, 3.
While he calls it a vaccine, Mamula’s therapy does not prevent cancers. It does reduce the tumor, however, and is successful at more than twice the rate of standard treatments, he said.
In dogs with osteosarcoma, a bone cancer, “about 70% of them will not survive 12 months,” Mamula said. “So that means there are 30% or so of these cancers in dogs that will survive 12 months, 30, 35%. We’ve increased that survival outcome to about 60, 65%.”
Kneisel said Ranger began limping when he was 7 years old and he had to amputate a leg. “I was reluctant to do that. I did not want to have amputation, didn’t want a tripod dog,” he said. “But it got to the point where it had to be done and so he had an amputation.”
After four rounds of chemo, it was found the cancer had spread to Ranger’s lungs and he was given six months to live. Then he found one of Mamula’s clinical trials at Ohio State University.
“My vet was willing to give the vaccine to Ranger … and he got those in November 2019. … So I took him back to Ohio State to have X rays done right before Christmas. … And when they took the X-rays, they told me that, well, the tumor had become stagnant, that it was not growing anymore, that it had stopped growing.”
Two months later, with more X-rays, Kneisel was told, “the tumor was completely gone, that it had been resolved. And you know, it’s a miracle.” Ranger lived another 3½ years and died in January.
Mike Rossa of Bayville, N.J., had a similar experience with his Carolina shepherd, Codi, who also had a leg amputated and underwent chemo.
A few months later, however, “another X-ray showed he had a golf ball-sized tumor in his lung. It had metastasized from his bone to his lung,” he said. At the time, the trial was being held in Norwalk, so Rossa brought Codi to Connecticut.
“And then I noticed eight months later, I know it sounds strange, but I noticed, you’re still alive,” Rossa said. “And I was kind of like, it’s odd, you know, by now osteosarcoma should have killed him.
“So we took him back up to Connecticut and they did an X-ray and the tumor was gone,” he said. “It was amazing. Even the vet that was in the trial couldn’t believe it when he saw the X-ray. He says, it’s gone. So he lived another 3½ years and then he died, unfortunately, from another cancer.”
Rossa now runs a Facebook page, where people tell their stories about their experiences with canine cancer and Mamula’s therapy.
During the treatment, the dogs get two injections, three weeks apart. “It triggers an immune response, antibodies in particular, that hopefully seek out and bind to proteins on the tumor, on the surface of the tumor, and start to kill it or inhibit growth,” Mamula said. “And either of those things are good.”
Mari Maeda began the nonprofit Canine Cancer Alliance after her three golden retrievers got cancer. The alliance is now helping support Mamula’s work.
“Osteosarcoma is a death sentence,” she said. “With surgery and chemo you could get about 12 months, maybe. If you’re lucky, maybe longer. But cancer does spread. It’s just like human osteosarcoma. It’s deadly. But with his vaccine, some dogs are living longer and some dogs with metastasis also became ‘cured.’ Cancer went away, which is really unheard of.”
Now they are working to help improve the immunotherapy.
“Quite a bit of funds that we’ve raised has been supporting his work,” Maeda said of Mamula. “We understand the limitations of his vaccine. But we also see that it’s very promising because it’s safe. It is effective for some of the dogs and it is potentially extremely affordable.”
The work definitely can extend to human cancers, Mamula said.
“Once it gets into human clinical trials, that’s probably where I will license, or Yale will license technology to others that are best equipped to do human clinical trials,” he said. “Yale has an active program for doing that, but that’s a bit outside of my expertise. I’d obviously be involved with that.”
Mamula is content with working on canine cancers, though.
“As far as hands-on work, the canine work is not only needed by the community or by pet owners in general, but also just an interest of mine,” he said.
He said he gets emails from people who may have lost a spouse and how their dog has cancer and they are asking for help.
“Or I get emails from those same people that say, My dog’s doing great and it’s now a year or two later and the vet said they were going to survive maybe two months or six months, and now it’s two or three years later and you know, gosh, thanks,” he said.
“So that’s what allows me to sleep at night and that’s what’s fun, honestly, about the project,” he said.
Ed Stannard can be reached at estannard@courant.com.
