German Shepherd Dogs May Benefit from Osteosarcoma Research of Vaccine Therapy & Immune Responses

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Based on radiographs and her veterinarian’s diagnosis, Julia Priest of Galt, California, believed that her 10-year-old German Shepherd Dog “Jessy” had torn the cranial cruciate ligament in her left stifle joint. A versatile performance dog, Herret’s Fire Jessy von Sontausen CDX TD BH PT JHD had earned titles in obedience, tracking and herding. Now in pain, Jessy had morphed into a couch potato not wanting to put weight on the hurt leg. Priest consulted a specialist about the leg. Radiographs indicated osteosarcoma.

“Sadly, the cancer was advanced, and nothing could be done for Jessy,” Priest says. “The timeframe from the original diagnosis to euthanasia was approximately six months, though the cancer progressed rapidly over the last eight weeks of her life. Jessy lived to be 11 years and 34 days of age.”

Osteosarcoma, or bone cancer, is a tough, challenging malignancy. No one knows exactly what causes osteosarcoma; however, large and giant breeds are considered to be at higher risk due to their size and weight. Standard treatment for the aggressive, most common primary bone cancer in dogs is surgical amputation of the affected leg followed by chemotherapy to help slow the development of metastasis.

The gravity of canine osteosarcoma and its devastating effect on dogs and their families have prompted the American German Shepherd Dog Charitable Foundation Inc. (AGSDCF) to support research at the University of Florida investigating a vaccine therapy and to fully fund an AKC Canine Health Foundation Clinician-Scientist Fellowship allowing a medical oncology resident at the University of Minnesota to investigate the unique DNA methylation patterns that characterize the immune cells present in osteosarcoma tumors.

GD3-Based Vaccine
Efforts to develop a life-extending vaccine for dogs with osteosarcoma that can be used as an adjuvant immunotherapy with standard of care treatment was the purpose of the two-year study at the University of Florida. Lead investigator Rowan J. Milner, BVSc, MMedVet, PhD, DACVIM (Oncology), DECVIM (Oncology), professor and director of Clinical and Translational Research, conducted a vaccine clinical trial to evaluate the effectiveness of a nanoscale liposomal disialyl-ganglioside (GD3)-based vaccine.

Found on the cellular surfaces of normal neural cells and melanocytes, GD3 is also highly expressed on osteosarcoma and melanoma cells and is believed to enhance malignancy in cancers and thus is being tested as a tumor antigen for immuotherapy.

This is a unique study as most immunotherapies are given after chemotherapy is complete. We wanted to capture those dogs that typically get metastases during chemotherapy,” Dr. Milner says. “Approximately 30 percent of the vaccinated dogs lived significantly longer than the dogs receiving the standard of care treatment only.”

Characterizing Immune Cells
Caroline Wood, DVM, PhD, a recent medical oncology resident at the University of Minnesota whose AKC Canine Health Foundation Clinician-Scientist Fellowship is funded by AGSDCF, is focusing on the immune system of osteosarcoma by looking at the DNA methylation patterns of lymphocytes, the main immune cells in the body.

“DNA methylation is a biological process by which a molecule acts as a chemical tag on DNA, which can alter the expression of the gene without changing its sequence,” Dr. Wood explains. “This leads to either increased or decreased transcription, and usually changed activity of the gene. The goal of this study is to further characterize the specific types of memory T-lymphocytes that help the immune system kill cancer cells present in osteosarcoma.”

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