Osteosarcoma is the most common bone cancer to affect dogs. It is a painful and aggressive disease. Affecting more than 10,000 dogs annually, predominantly larger breeds, it kills more than 85 percent within two years.
Nicola Mason, a researcher and veterinarian at the University of Pennsylvania School of Veterinary Medicine, is working to put a dent in those figures. Since she was a postdoctoral fellow in the laboratory of Carl June, the Perelman School of Medicine researcher behind the breakthrough CAR-T immunotherapy for treating blood cancers, Mason has steadily pushed forward the field of immunotherapy in the veterinary arena.
A new $775,000 grant from the Morris Animal Foundation will help her build on her past successes to test a vaccine that could improve longevity and quality of life for dogs with osteosarcoma. Mason's team will conduct clinical trials to evaluate a novel immunotherapy treatment which combines a molecule expressed by cancer cells with a modified live form of the bacteria Listeria monocytogenes.
A pilot study demonstrated that this combination elicited a powerful, targeted immune response directed against osteosarcoma cells.
"We know that the traditional standard-of-care treatments we use for osteosarcoma are not effective at eliminating all tumor cells because the majority of dogs still die from metastatic disease," Mason says. "This immunotherapeutic approach is very promising as it stimulates the patient's own immune system to seek out and specifically kill cancer cells that remain after traditional standard-of-care therapy."
The prevailing treatment for osteosarcoma consists of amputation followed by chemotherapy. Though the primary tumor is often vanquished with this approach, it typically fails to prevent the spread of cancer cells to other organs, leading to deadly metastasis of the disease.
The vaccine supplements standard treatment by attacking these stray cancer cells before they can cause problems. The vaccine is a highly attenuated Listeria bacteria that is genetically modified to express a tumor marker expressed by the osteosarcoma cells. After receiving the vaccine, the patient's immune system is activated by the Listeria and then directed to recognize cells that express the osteosarcoma marker, eliminating them and thus removing the cells responsible for relapse.
Researchers tested the vaccine in a pilot study with 18 dogs. Those that received the vaccine lived more than twice as long as the historical, matched, control group, with median survival times of 956 days compared to 423 days.
The current prospective, controlled, clinical trial, funded by the Morris Animal Foundation and performed through the Comparative Oncology Trials Consortium at the National Institutes of Health, will evaluate this novel immunotherapy in 80 dogs at 11 of the top, university-based veterinary centers across the United States, including Penn. The study will compare the immune responses and overall survival of immunized dogs to a group of dogs that received standard of care alone. The study also will address the ability of the immunotherapy to retard metastatic disease in enrolled patients that develop metastatic disease prior to their scheduled receipt of the immunotherapy.
Nicola Mason is an associate professor of medicine at the University of Pennsylvania School of Veterinary Medicine
Katherine Unger Baillie