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Dogs teach medical science new tricks

New treatments that help dogs with cancer also help people.

March 26, 2014

At 14 years of age, Piper was looking well. A little old, maybe, but showing the good spirits she and other golden retrievers are famous for—and all despite her having brain cancer.

That was back in 2009, when Piper was making a public appearance on the day she received the last injection of a vaccine made from her own tumor. She also met John Huls, a St. Cloud resident and fellow brain cancer patient who was being treated with a similar vaccine for humans, based on work with Piper and other dogs.

Their meeting symbolized how insights gained from treating canine cancer are being translated to humans. The work, carried out through the Masonic Cancer Center, University of Minnesota, is still new but promising, and brings together researchers and clinicians in veterinary and human medicine.

At the center of the double initiative stands Jaime Modiano, a professor of veterinary medicine and director of the Animal Cancer Care and Research program in the U's College of Veterinary Medicine.

"The clinical picture in dogs and humans is very similar," he says. But because of dogs' shorter lifespans, "we can get answers in two years instead of 10 years. And we're also helping the dogs.”

Cancer vaccines

So far, researchers have focused on brain and bone cancers, which can afflict both dogs and people. In one approach, they create a vaccine using the canine patient's own tumor cells, as was done with Piper. This method originated with two University researchers: veterinary surgeon Elizabeth Pluhar and immunologist John Ohlfest, who died in January 2013 from malignant melanoma.

Before being used for a vaccine, tumor cells must be grown in culture. Pluhar and Ohlfest weren't the first to make vaccines from a patient's cells, but only they had the insight that since tumors grow in low-oxygen environments in the body, their cells should be cultured under low-oxygen conditions.

"This environment made them look more like tumors to the immune system, not artificial cells in culture," Modiano notes.

Pluhar and Ohlfest's approach worked so well on dogs that the FDA gave it accelerated approval for testing in humans. The first trial, with eight brain cancer patients (including Huls), used a modified method developed by Michael Olin, Christopher Moertel, and Ohlfest, all of the Department of Pediatrics, along with several colleagues.

Vaccines are built on the fact that tumor cells are coated with certain "antigens"--biomarkers for cancer. In the body, immune cells called dendritic cells remove these antigens and present them to other immune cells called T cells, like presenting a scent to a bloodhound. Then the immune system begins a search-and-destroy mission.  

In the human trial, the vaccine contained patients’ dendritic cells that carried tumor antigens and had been treated to boost their ability to turn on the immune system. Huls, who joined the trial after conventional treatments had made him feel very sick, said the vaccine treatment really helped. 

"We showed that the vaccine in people generated a therapeutic response," says Moertel. Of Huls, who died last year, he says, “We believe it definitely prolonged his life by at least a year,” adding, “We have opened a second trial, focused purely on children with a brain tumor called DIPG, which to date has been universally fatal."

A better prognosis

Researchers have wondered if there are genetic markers within tumors that signal how fast they will kill a patient.

Using data from children with bone cancer around the world, researchers elsewhere looked for, but couldn’t find, markers in the tumors that would predict how long a child would live. But when Modiano and colleagues studied bone tumors from various dog breeds, they did find markers that correlated with the dogs’ survival time. They also found the same markers in the children’s data.

Because humans are so diverse, there was too much genetic ‘noise’ for the markers—which are just patterns of gene activity—to show up. “But within a dog breed, the genetic noise is lower, so they were clear,” he says. “Then with the children’s data, we knew what to look for.”

This discovery could guide children's physicians, who may want to use tumor markers to identify those patients who need more aggressive treatment, and those whose less ferocious tumors may allow their doctors "to let up on the pedal a little bit and decrease the side effects," Modiano says. 

As a veterinarian, Modiano is committed to helping four-footed patients, but his vision goes way beyond that.

"Cancer is the monster in the closet, and everybody is afraid of it," he says. "We think that by turning on a light and showing what the monster looks like—that is, understanding it—it’s a first step in removing fear. Our program's vision is to create a world where we no longer fear cancer."

Contact the writer at morri029@umn.edu

 

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