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University of Pennsylvania researchers enlist dogs in cancer study

Nicola Mason, a veterinary immunologist at the University of Pennsylvania walks Sasha, who lost a foreleg to bone cancer.

Philadelphia Inquirer

Nicola Mason, a veterinary immunologist at the University of Pennsylvania walks Sasha, who lost a foreleg to bone cancer.

Sasha is still spunky at 12 — a white dog with a smattering of black, floppy ears and a sweet face. Even after she lost her right foreleg to bone cancer, her owners said, she could jump and catch a Frisbee. Unfortunately, in nearly all cases like Sasha's, the surgery offers just a short respite before the cancer comes roaring back. Her only hope now lies with an experimental treatment — and if it works, it could next be tested on humans with this type of bone cancer, known as osteosarcoma.

Doctors at the University of Pennsylvania's School of Veterinary Medicine recently pumped a modified listeria bacteria into Sasha's bloodstream, hoping to push her immune system to kill remaining cancer cells.

While animal research has long played an important role in human medicine, an increasing number of clinical trials for dogs are being designed to help both species. Right now, the vast majority of cancer treatments that work in mice fail in people, said immunologist Carl June, director of translational research at Penn's Abramson Cancer Center. By testing the treatments in dogs, he said, veterinarians are helping sort out the potential winners.

Osteosarcoma is also easier to study in dogs because it's relatively common, especially in larger breeds. In humans, it's an orphan disease, but it takes a vicious toll. It strikes young people, most of them between the ages of 13 and 25. Often their only hope for survival is a radical amputation.

Liliana Ruano said she and her husband, Carlos, wanted a dog that could accompany the North Carolina couple on hiking and camping adventures, and Sasha turned out to be just perfect. They often visit Carlos's family in Pennsylvania and hike with Sasha.

But earlier this year, Sasha started limping. An X-ray revealed bone cancer, and the doctor offered grim choices. They could do nothing and their faithful hiking buddy would die in agony, or they could amputate the leg, which would give her a few months of pain-free life before the cancer returned, usually as a fatal chest tumor. Mild chemotherapy would extend her life slightly.

They opted for the surgery and chemotherapy, and Sasha came through so well she's again playing Frisbee. Concerned about a recurrence, Liliana found information about the Penn trial on a Facebook page about dogs and cancer. Treatment with listeria bacteria might sound scary because it's associated with food poisoning, but it is disabled so that it is harmless, yet still provokes an immune response.

Modified listeria has been tested in mice and used in some trials connected with human cervical cancer, said Penn veterinary immunologist Nicola Mason. For this treatment, the listeria was also genetically modified to allow the bacteria to make a protein called her2/neu — the same one expressed in Sasha's tumor.

The idea is to train the patient's immune system with the her2/neu protein the way you might train a bloodhound. The immune cells are geared to attack listeria, but they will also be trained to recognize and attack cancer cells that express the her2/neu. This protein is one of the few marks that distinguishes the cancer cells from healthy ones, so the immune system should go after the cancer.

Though Sasha looks healthy now, amputations almost always leave behind a few malignant cells, which is why dogs almost always get a fatal recurrence.

"They are sitting on time bombs," Mason said. In virtually all cases, stray malignant cells eventually spread to the lungs and kill the dog. "What we're doing with the immunotherapy is mopping up the cancer cells we can't see," she said. So far, they've signed up six dogs, and they aim to recruit 9 to 18.

Carl June sees clinical trials with dogs as a way to test promising new approaches to fighting cancer and to accelerate the process of sorting the winners from the losers.

No other large animals routinely get cancer the way dogs and humans do. Monkeys rarely get cancer spontaneously, and many people have ethical concerns about giving cancer to fellow primates. Scientists see some striking similarities in the genetics and biology of dog and human cancers. Cats, too, are starting to be entered in clinical trials, but Mason said dog research is further ahead.

University of Pennsylvania researchers enlist dogs in cancer study 07/25/12 [Last modified: Wednesday, July 25, 2012 7:50pm]
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