How a dog’s life may change the course of cancer in people

Don’t let her old-soul brown eyes and prematurely gray fur fool you. Jellybean is a spirited 4-year-old Labrador Retriever mix who is considered a rock star among the dozens of dogs enrolled in cutting-edge cancer research at Tufts University’s Cummings School of Veterinary Medicine.

© Suzanne Kreiter/Globe Staff Zachary Mendonca carried Jellybean into Foster Hospital for Small Animals at Cummings School of Veterinary Medicine at Tufts University.

The research, part of President Biden’s Cancer Moonshot initiative, aims to improve treatments for dogs, as well as people, diagnosed with the disease.

Jellybean’s remarkable story began with a tiny bump on her right rear leg in June 2020 that swelled to the size of a baseball within three weeks. She was diagnosed with an aggressive and often deadly form of bone cancer.

Amputation and traditional chemotherapy didn’t halt the disease’s insidious progression to her chest. Typically, dogs with bone cancer live only eight to 10 weeks once the cancer spreads to their lungs, even with treatment. An estimated 15,000 dogs a year are diagnosed with bone cancer.

Determined to not give up, Patti and Zachary Mendonca enrolled their beloved pet in a trial at Cummings that was exploring different combinations of drugs for dogs with advanced osteosarcoma, the type of cancer that Jellybean had.

“You can’t quit,” said Zachary Mendonca. “Life is full of hurdles, hoops, and inconveniences. But if there’s a little hope ... you have to go for it.”

Jellybean’s treatments started in November 2020, and by late December the tumors in her chest started to shrink. By February, they had disappeared. She still takes the experimental medication.

Now researchers are digging deeper to understand how Jellybean’s extraordinary remission may prove helpful for people, particularly children, who develop a similar bone cancer.

None of the other 50 dogs in the trial stayed in remission nearly as long as Jellybean. They have all since died. Their median survival time was about five months, compared to the two to three months for dogs that receive traditional chemotherapy.

“When we have a better understanding of why some dogs [like Jellybean] do well and others don’t, it’s going to allow us to layer on additional treatments to enhance the response that we’ve seen,” said Dr. Cheryl London, the Cummings School’s associate dean of research and graduate education who oversees clinical trials.

Unlike mice and other rodents typically used in research, dogs live in our same environment. And their immune system is similar to those of people.

“So that’s sort of the nice thing about using dogs as a model system to ask and answer questions about treatment approaches that may have value on the human side,” London said.

Dogs are diagnosed with many of the same or very similar cancers found in people, including breast, bladder, and bone cancer, as well as lymphoma. And, as with people, researchers are increasingly looking toward, or designing drugs, that may stimulate a dog’s immune system to recognize and attack cancer cells, rather than use chemotherapy, which often wreaks havoc on many healthy cells.

“Chemotherapy is like taking a firehose to water a houseplant; it attacks any fast growing cells and in areas other than the tumor,” said Dr. Laura Venner, an oncology intern at Tufts who is working on the bone cancer trial.

Immunotherapy is much more targeted. The drugs are designed to wake up a patient’s immune system and teach it to recognize and specifically destroy cancer cells, while leaving other cells intact.

The trial that Jellybean was in used a three-drug combination, including a blood pressure drug used in humans that has shown cancer-fighting properties and an investigational drug, not yet approved for people or pets, that is being studied in diabetes trials.

For more than two years now, the Mendoncas have driven more than an hour from their North Kingstown, R.I., home to the Cummings School in Grafton each month so researchers can track Jellybean’s progress and take X-rays and blood samples.

About a year ago, the researchers launched a new trial.. Instead of enrolling dogs like Jellybean, who had had amputations and then failed chemotherapy, they are now enrolling dogs with bone cancers that have not yet spread and giving them the triple-drug combination for two weeks before amputation.

“Doing this before the tumor is removed is probably really important to recondition the immune system” to recognize the cancer cells, London said.

Then the dogs stay on the drugs. But for how long?

“That’s the question of the day,” London said. “At first we were like, ‘Oh, we’ll stop at six months. And then the dogs, some of the dogs, just kept going. So we were like, ‘Oh, we’ll stop at a year. And now we’re like, ‘We’re not stopping.’”

At the same time, scientists across the country are studying other immunotherapy approaches for translating dog cancer treatments to people.

Dr. Nicola Mason, a professor of medicine at the University of Pennsylvania School of Veterinary Medicine, is using listeria, a bacteria often associated with food poisoning, in her research with dogs.

“We learned that listeria is really good at waking up the immune system,” she said.

The researchers genetically altered the listeria to a weakened form that won’t make patients sick. Then they pinpointed a protein that’s associated with bone cancer and added it to the weakened listeria.

When this immunotherapy enters a patient’s body, it wakes up the immune system and tricks it into thinking the cancer protein is listeria that it needs to fight off, and it attacks the cancer in the patient’s body.

The researchers only work with dogs who have been diagnosed with cancer and whose owners consent to the treatments.

The knowledge gleaned by Mason and other researchers is now being used in a listeria trial involving children and young adults with bone cancer.

Similar to the listeria treatment, the three-drug therapy still given to Jellybean has produced few side effects other than to turn her once-jet black and tan fur predominantly gray. She eagerly scarfs the pills, wrapped in treats, morning and night.

”If we miss it by one minute, she is on top of me,” said Zachary Mendonca.

When Jellybean was first diagnosed in 2020, COVID-19 closures meant families were not allowed into hospitals to say their goodbyes to people or pets. Given the grim prognosis for Jellybean at that time, the Mendoncas feared the worst.

”I watched many people saying goodbye over the phone” at the Rhode Island hospital where Jellybean was initially treated, Patti Mendonca said.

Then when they enrolled Jellybean in the Tufts trial that fall, the Mendoncas understood the chances of her survival were limited.

“At that point, we were just thinking, maybe she will just help another dog for the future,” Patti Mendonca said.

Now researchers think Jellybean’s amazing odyssey holds important clues.

“Jellybean continues to surpass our expectations and remains cancer free after her December recheck appointment,” London, the lead Tufts researcher said. “We are thrilled that her success story continues, and we’ll keep monitoring her and using what we learn from her response to the trial to inform future treatments.”

“I don’t think I can go to Vegas,” he said, “cause all my luck is tied up in this dog.”