December 01, 2017

 

 Vaccine holds promise for treating osteosarcoma in dogs

Posted Nov. 15, 2017

Veterinarians in the audience wanted to know when they could get their hands on the new treatment.

Dr. Sue Ettinger, a veterinary oncologist, had mentioned a promising vaccine for osteosarcoma in dogs when she presented "Osteosarcoma Survival Guide" at AVMA Convention 2017 this past July in Indianapolis.

A study by Dr. Nicola J. Mason in 18 dogs with osteosarcoma but free from gross metastatic disease found that the median survival time was 956 days with the vaccine, compared with 423 days in a historical control group. At press time, Aratana Therapeutics Inc. hoped to receive a conditional license for a freeze-dried version of the vaccine by year's end from the Department of Agriculture's Center for Veterinary Biologics.

Dr. Mason, an associate professor of medicine at the University of Pennsylvania School of Veterinary Medicine, is expanding the pilot study to a study of 80 dogs at multiple sites, with funding committed by Morris Animal Foundation. 

Dr. Nicola J. Mason, an associate professor of medicine at the University of Pennsylvania School of Veterinary Medicine, is studying a Listeria-based vaccine to treat dogs with osteosarcoma.​ (Courtesy of the University of Pennsylvania School of Veterinary Medicine)

Osteosarcoma in dogs is similar to the disease in children in terms of initial signs, progression, and propensity for metastasis as well as possibly the presence on tumor cells of the HER2/neu receptor, which is present in certain other cancers. Yvonne Paterson, PhD, a microbiologist at the university's medical school, has developed an experimental vaccine using an attenuated Listeria strain to target HER2/neu, originally focusing on human patients with other HER2/neu-positive cancers such as breast cancer. The data in mice were very promising.

In the field of veterinary medicine, "We all recognize the need for better, safer, kinder, and more effective treatments for dogs with cancer," Dr. Mason said. "And this need is clearly evident in osteosarcoma."

Researchers have speculated that osteosarcomas in dogs are usually HER2/neu-positive, although this is still a matter of debate. Dr. Mason said about 70 to 80 percent of osteosarcoma tumors that have been examined in her laboratory have positive staining by immunohistochemistry using a polyclonal anti-HER2/neu antibody.

The pilot study of the vaccine involved dogs with appendicular osteosarcoma that was found by immunohistochemical methods to be HER2/neu-positive. Dogs in the experimental group underwent amputation, follow-up chemotherapy, and then vaccination. Dogs in the historical control group had only amputation and follow-up chemotherapy. Dogs in both groups had minimal residual disease following chemotherapy.

"We know that most of these dogs relapse with metastatic disease, so clearly cancer is left after chemotherapy," Dr. Mason said. "And we were asking the question: Could this vaccine induce an immune response which would eliminate those remaining cancer cells?"

The vaccine was created by removing many of the virulence genes from the Listeria organisms and genetically modifying the bacteria to express HER2/neu. The immune system attacks the attenuated Listeria organisms and learns to kill other cells that express HER2/neu, including osteosarcoma cells, at least hypothetically. Although other healthy cells do express HER2/neu, the pilot study did not find any evidence of targeting of other tissues.

The first two dogs in the pilot study are alive as of this writing in October. Scooby Doo was found to have osteosarcoma on May 1, 2012, and Dolly on June 1, 2012. Other dogs are alive after four to 4 1/2 years. The survival rate was 67 percent at two years and 50 percent at three years. Some dogs did not respond and died of metastatic disease. So now one question is: Why do some respond and others don't—and is it possible to predict responders versus nonresponders?

These dogs live normal lives. They have an excellent quality of life. If you look at these dogs, other than the fact that they are missing a limb, you wouldn't know anything's wrong with them."

Dr. Nicola J. Mason, associate professor of medicine, University of Pennsylvania School of Veterinary Medicine

Dr. Mason said: "These dogs live normal lives. They have an excellent quality of life. If you look at these dogs, other than the fact that they are missing a limb, you wouldn't know anything's wrong with them." She has pictures of the dogs all around her office.

The pilot study was part of a program by biotechnology company Advaxis Inc. to develop a Listeria-based vaccine to target various HER2/neu-expressing cancers. Advaxis licensed the product to Aratana Therapeutics, which is developing and manufacturing the vaccine for dogs.

Dr. Ernst Heinen, a veterinarian who is chief development officer for Aratana, said the Advaxis product is frozen, not a good way to distribute a product on the veterinary side. Aratana created a freeze-dried product to distribute at refrigerated temperatures.

Receiving a conditional license from the USDA would give Aratana the opportunity to start commercialization of the vaccine for osteosarcoma in dogs but not under a brand name. The vaccine is administered as three doses two weeks apart with boosters every six months.

Starting out, the company will provide the product to certain clinics to run an additional safety study in the field, a necessary step to apply for full licensure. Aratana is working on being ready soon to start manufacturing and distribution.

"This technology is very exciting for everyone; it's something completely new," Dr. Heinen said. He said veterinarians "are eagerly awaiting for the product to be released."