Research's best friend

Posted: November 12, 2007

Eileen Eisenhower noticed the golf-ball-size lump on the hind leg of her beloved dog and immediately knew it was a cancerous lymph node.

At age 8, Kyra was in late middle age, prime time for lymphoma to strike. What's more, one of the Rhodesian ridgeback's siblings had recently undergone chemotherapy for the disease.

Eisenhower and her husband, Brian, were reluctant to put Kyra through such toxic treatment. Even if it worked, they knew the cancer would probably return and kill her within a year.

But then the Pennsauken couple read online about an immune therapy - a supplement to chemotherapy - being developed by the University of Pennsylvania's School of Veterinary Medicine and its Abramson Cancer Center. If this novel "cancer vaccine" worked well in dogs with lymphoma, it would eventually be tested in children with the human equivalent, non-Hodgkin's lymphoma.

Kyra became the first dog to test the vaccine.

Now, almost two years later, the sleek, honey-brown hound with a ridgelike cowlick on her back seems to be cured. Of nine other dogs treated so far, three have been healthy for more than a year.

And their humans are doubly happy.

"I'm a nurse and I've taken care of children with lymphoma," Eisenhower said last week, stroking Kyra. "Maybe someday I'll be giving the vaccine to a child."

Penn oncologist Robert Vonderheide, a leader of the vaccine study, said, "Dogs and humans share a lot of the same biology. Like the vet school motto says: 'Many species. One medicine.' "

Man's best friend is becoming increasingly important to the study and treatment of human cancers. One indicator is a new research program launched by the National Cancer Institute in 2003 to improve human cancer-drug development by using dogs and cats as comparative models.

As part of this "comparative oncology" initiative, the institute set up a new consortium of veterinary medicine schools - including Penn's - that will conduct clinical trials of experimental treatments.

"Dog cancers capture the 'essence' of the problem of human cancer in a manner not possible with other animal model systems," notes Chand Khanna, head of the cancer institute's comparative oncology program.

Cancer researchers have long taken advantage of the similarities between canine and human anatomy and physiology. A big difference has also been beneficial - dogs age faster, so studies produce results more quickly. Fifty years ago, dogs helped pioneer the concepts and techniques for human blood stem-cell transplants, also known as bone marrow transplants.

"The dog has contributed to a legacy that saves thousands of patients annually," Seattle cancer researcher Rainer Storb wrote in a recent article about cell transplantation in the journal Veterinary and Comparative Oncology.

While comparative oncology goes way back, several recent advances have spurred the field. Experts point to the sequencing of the canine genome in 2005, and the advent of "targeted" cancer therapies for humans.

Targeted drugs disrupt the molecular machinery of cancer cells; conventional chemotherapies, by contrast, poison fast-dividing cells, both healthy and malignant. Chemo is more toxic, but easier to test in humans.

The National Cancer Institute says dogs can help researchers figure out dosing, side effects, and, most of all, whether a targeted drug is hitting its molecular mark - or not worth pursuing.

Unlike laboratory mice, which are genetically manipulated and induced to develop human cancers, dogs are naturally affected by prostate, breast, bone and other cancers that closely mimic the human versions. In addition, the potential pool of needy canines is vast. Of the estimated 70 million pet dogs in this country, four million are diagnosed with cancer each year.

Many humans are willing to go to great lengths - not to mention expense - to prolong the lives of their four-legged family members.

"Why not transform the cancer toll in pet dogs from something that is only a sorrow today into a national resource, both for helping other pets and for aiding people?" Purdue University comparative oncologist David J. Waters wrote in a Scientific American article last year.

Lymphoma, one of the most common and aggressive canine cancers, takes a particularly high toll.

Without treatment, dogs usually die within a few months. Even when they receive the same chemotherapies as humans - at a cost of up to $5,000 - most have just a brief remission and die on average 11 months after diagnosis. Only about 15 percent are cured with conventional therapy.

Kyra's sibling was not one of the lucky ones.

"The point is, we need more than chemotherapy," said Karin Sorenmo, chief of oncology at Penn's vet school.

She and a colleague, Penn veterinarian Nicola Mason, were eager to see if Vonderheide's cancer vaccine could be used after chemotherapy to keep the cancer from coming back so soon.

A number of drug companies are developing therapeutic cancer vaccines for humans, but none are yet approved in the United States. Unlike conventional immunizations, which prevent disease by priming the immune system to attack an infectious invader, the new vaccines are designed to make the immune system fight cancer after it arises.

This is quite a feat because cancer is made of the body's own out-of-control cells; in effect, the vaccine must trick the body into attacking itself.

During four years of research, Vonderheide had achieved promising results - but only in lab dishes. Kyra, diagnosed with the most advanced stage of lymphoma, was the real deal.

After getting approval from an ethics review committee at Penn, the researchers removed infection-fighting B cells from a sample of Kyra's blood. Then they extracted genetic material called RNA from their furry patient's lymphoma cells. With a bit of molecular technology, they slipped this RNA into the B cells.

They hoped that these modified B cells, when returned to the dog's body, would act like tattletales, telling her immune system how to recognize and attack any lurking lymphoma cells.

And that's what apparently happened.

"We were incredibly delighted," Vonderheide said. "We know we can improve the vaccine. But to have promising results with our very first formulation was very encouraging."

The treatment - three vaccine shots a week for three weeks, plus various scans and tests - was free to the Eisenhowers. By the end, Kyra had regained most of the 10 pounds she lost while undergoing four months of chemotherapy. She was her usual squirrel-chasing, sofa-crowding, bacon-begging self.

"She's very sweet," Eisenhower said last week as Kyra sat obediently - waiting to be rewarded with a bit of bacon.

Six dogs in the trial did not respond to chemotherapy, so they did not receive the vaccine. Four of the nine dogs who got the shots, including Kyra, have been in remission for a year or more - a better rate than would be expected with chemo alone.

The numbers are too small to draw conclusions, but good enough to expand the study, which is being funded by the nonprofit Alliance for Cancer Gene Therapy.

"We have a long way to go, but we're encouraged," Vonderheide said. "If this works, it's possible the approach could be used in kids and adults with any type of cancer."


More about this and other canine cancer research:

Contact staff writer Marie McCullough at 215-854-2720 or

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