After finding remarkable success in canine companions, U team opens a new clinical research study for human patients facing deadly brain tumors
One morning last March, Huck, a sweet, two-and-a-half-year-old Brindle, was out for a walk when he had a seizure. Panicked, Huck’s owners rushed him to the veterinarian and were relieved when all of his blood tests came back normal.
But when Huck had another seizure the next day, deeper investigation revealed the grim cause: Huck had a brain tumor that closely resembled human glioblastoma, an aggressive brain cancer. The veterinarian estimated that Huck had about three months to live.
“We were devastated,” says Robyn Porter, who’d brought Huck into her family when he was just 10 weeks old. “He’s the kindest, most gentle dog we’ve ever had, he’s just two-and-a-half, and he’s got a brain tumor? The diagnosis could not have been worse.”
Huck’s story took a dramatic turn, though, when Porter and her husband, who live in the Washington, D.C., area, heard about an experimental treatment being offered at the University of Minnesota.
There, veterinary surgeon G. Elizabeth Pluhar, D.V.M., Ph.D., a professor in the College of Veterinary Medicine, was working with U colleagues to develop treatments for dogs that have this type of brain tumor. And while the Masonic Cancer Center group was still collecting data, the results of her studies were promising.
“We’re not curing dogs of these aggressive brain tumors yet, but we’re extending their lives, sometimes significantly,” Pluhar says. In fact, most dogs in the study survive for an additional 14 months, with a handful living more than 30 additional months.
“And during treatment,” she adds, “the dogs have an excellent quality of life.”
But will the treatment that’s helped so many dogs like Huck work in humans? That’s what University physicians and scientists aim to find out as they give people with recurrent glioblastoma their novel immunotherapy for the first time through a clinical research trial. This first-ever study launched in January, and so far four human patients have received the therapy.
In recent years, scientists have discovered key similarities between brain tumors in dogs and people, giving the U’s team a glimmer of hope that they’ll see good results in humans, too.
“Unfortunately, man’s best friend shares more with people than just extraordinary bonds of friendship,” Pluhar says. “The rate of malignant brain tumors in dogs is similar to that in humans—and we haven’t identified another species that develops these tumors at this rate, just dogs and people.”
Their tumors also share the same type of genetic mutations, Pluhar adds, making studies like hers valuable road maps to developing new therapies for humans. Those therapies are desperately needed, as today just 5% of people diagnosed with glioblastoma survive five years or longer.
Seeing the target
Back in 2012, the U of M Medical School’s Michael Olin, Ph.D., first recognized that people—as well as laboratory mice—with this type of brain tumor had sky-high levels of a protein called CD200. Because such high levels of this protein worked to shut down the body’s natural immune response to foreign invaders like cancer cells, Olin zeroed in on developing an intervention that targeted CD200.
“Our treatment activates cells in a way that stimulates the body’s antitumor response,” Olin says, “and at the same time inhibits the tumor from putting the brakes on the immune system.”
Olin works closely with Christopher Moertel, M.D., a professor in the Medical School’s Department of Pediatrics and medical director of the pediatric neuro-oncology program at M Health Fairview University of Minnesota Masonic Children’s Hospital.
Moertel is optimistic that Olin’s research has put them on the right track to finally offer some hope to people facing glioblastoma.
“Every cancer that kills people has figured out how to fool the immune system, how to erect barriers to treatment,” Moertel says. “Now we have both lab evidence and canine evidence that this immunotherapy approach enables the immune system to get around those barriers that brain tumors set up.”
Patients who have recurrent glioblastoma will receive a series of injections designed to rev up the immune system and attract cancer- fighting cells to the tumor site. Each patient will receive both the CD200 treatment and a brain tumor immunotherapy developed at the U a decade ago.
The combination, Neil says, will allow patients’ bodies to see the tumor cells more efficiently and break down the tumor’s defense systems.
“Glioblastoma has thwarted the best efforts of researchers and clinicians for far too long,” says Neil, an assistant professor of neurology in the Medical School. “But now we feel that this novel immunotherapy may finally give us the upper hand in successfully treating this aggressive cancer.”
Outpouring of support
Many individuals and philanthropic organizations have fueled the CD200 research in a way that Moertel calls “incredible.” Humor to Fight the Tumor, the Randy Shaver Cancer Research and Community Fund, Bob and Corrine Ferris, Shepherd Trust Fund, the Dahlberg Family Foundation, and Love Your Melon have all contributed to the work, as have larger organizations like Children’s Cancer Research Fund and Hyundai Hope on Wheels.
Even private investors in the biotechnology company OX2 Therapeutics, which started using the U-developed technology and is now sponsoring the human clinical study, are committed to the cause.
“So many people in our community have ownership in this work,” Moertel says. “I’m often astounded by how committed they are, and so grateful. We feel a deep sense of partnership with them.”
After taking part in Pluhar’s CD200 canine study, Huck happily chased chickens on the farm for almost nine months before he had another seizure in late November, a warning sign that his tumor was growing back. Now he’s had a second surgery and begun another round of immunotherapy under Pluhar’s care. And meanwhile, he’s still chasing chickens.
For Pluhar, being able to help dogs that develop these aggressive tumors, while at the same time gathering the urgent data necessary to help bring the treatment to humans, has been deeply rewarding.
“If we see these same results in people,” she says, “it’ll be the biggest breakthrough in treating glioblastoma we’ve ever had.”
Olin and Moertel believe the CD200 immunotherapy offers even more potential than its hoped-for impact on glioblastoma.
“We have preliminary data showing that CD200 works on melanoma, breast cancer, and bladder cancer, too,” Olin says. “We think this immunotherapy is going to be a rock star.”
Neither Moertel nor Olin can share the CD200 story without crediting the many, many people, inside and outside the University, who have contributed to the work.
“Private investors, generous philanthropists, scientists in immunology, informatics, molecular biology, veterinary medicine, and neuro-oncology … the level of collaboration has been incredible,” Moertel says. “This is why the University of Minnesota is an international leader in work that’s dedicated to killing cancer with the immune system.
“I believe there are even greater stories to come.”
Learn more about how your gift can advance the human study by contacting Jen Foss of the University of Minnesota Foundation at firstname.lastname@example.org or 612-626-5276 or the canine study by contacting Lauren Craft at email@example.com or 612-626-6501.