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Yale Researcher Develops Vaccine That Can Slow or Halt Certain Cancers in Dogs

The drug could also be used to treat humans in the future.

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(PRESS RELEASE) NEW HAVEN, CT — 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.

Two years ago, Hunter, who worked as a search-and-rescue dog for a decade, was diagnosed with osteosarcoma, a form of bone cancer that kills upwards of 65% of the dogs it afflicts within 12 months.

But now, thanks in part to a novel cancer vaccine developed by Yale researcher Mark Mamula, Hunter has no signs of cancer.

The treatment, a form of immunotherapy that is currently under review by the U.S. Department of Agriculture (USDA), has undergone clinical trials. 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. “If we can provide some benefit, some relief — a pain-free life — that is the best outcome that we could ever have.”

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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.

Researchers have found that in dogs, as is the case for humans, several types of cancer 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.

In developing the new 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, that 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 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.

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To date, more than 300 dogs have been treated with the vaccine through clinical trials that 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, they have found, the treatment also shrinks tumors. 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.

“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,” Mamula 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.”

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