DNA-based vaccine triples survival for dogs with melanoma

April 09, 2003

NEW YORK April 8, 2003 - The options for treating advanced melanoma are limited - regardless of whether the patient is a dog or a human. Because this deadly cancer is virtually resistant to chemotherapy and radiation in its late stages, new approaches are being investigated including vaccines that harness the immune system. For nine dogs that naturally developed canine malignant melanoma, treatment with a new DNA-based vaccine more than tripled their median survival from an expected 90 days to an average of 389 days.

The results of this collaboration between the dogs' veterinarians at The Animal Medical Center (AMC) and researchers at Memorial Sloan-Kettering Cancer Center where the DNA-based vaccine had undergone pre-clinical testing are reported in the April issue of the Clinical Cancer Research. The vaccine continues to be studied at AMC. A parallel clinical trial began last fall at MSKCC for people with high risk of melanoma recurrence.

"Most medicines that we use to treat animals are the same as those given to humans," explained Philip J. Bergman DVM, MS, PhD, Head of the Donaldson-Atwood Cancer Clinic and the Flaherty Comparative Oncology Laboratory at The Animal Medical Center and the study's first author. "This vaccine was first tested in the laboratory at MSKCC and then given to dogs with melanoma after receiving approval from the United States Department of Agriculture and the AMC's own Institutional Review Board. We felt it was useful to see if immunotherapy might help these very sick dogs with advanced melanoma since the response rates for standard chemotherapy were extremely poor with no evidence of improved survival."

Canine malignant melanoma (CMM) is the most common oral cancer in dogs and accounts for one out of twenty cancer diagnoses. It is highly aggressive, occurring spontaneously in the mouth, nail bed and foot pad. CMM is most successfully treated in its early stage by surgery. However, the prognosis is not good if there is a late diagnosis or the cancer has spread to another organ. In advanced stages, the median survival is 2 to 3 months.

In this study, nine dogs with advanced melanoma were given four bi-weekly injections of human tyrosinase DNA vaccine that was constructed at MSKCC's Gene Transfer and Somatic Cell Engineering Facility. The dogs were injected with the vaccine using the Biojector-2000, a needle-less delivery device. They showed no side effects or toxicities with only a mild inflammatory reaction observed at the injection site. Two showed no evidence of disease when they were checked after completion of the vaccine regimen. Four dogs survived for over 400 days with the longest survivor still alive after more than 615 days. The median survival was 389 days.

"Like humans, dogs develop melanoma spontaneously through an interaction of their genes with the environment," said Jedd D. Wolchok, MD, PhD, an oncologist on the Clinical Immunology Service at Memorial Sloan-Kettering and senior author of the study. "By conducting trials in humans and large animals that live in the same surroundings as humans and spontaneously develop cancers, there can be a synergy that we hope will result in improved cancer treatment for all."
The studies co-authors are Josephine McKnight, DVM, Andrew Novosad, DVM, Sarah Charney, DVM, John Farelly, DVM, Ann E. Hohenhaus, DVM, and Diane Craft, BS, of The Animal Medical Center. From Memorial Sloan-Kettering Cancer Center - Alan N. Houghton, MD, Chief, Clinical Immunology Service; from the Gene Transfer Facility - Michel Sadelain, MD, PhD, Director; Isabelle Riviere, Ph.D., co- Director; Yusuf Jeffers, and Michelle Wulderk, PhD; from the Laboratory of Tumor Immunology - Neil Segal, PhD , Polly Gregor, PhD , and Manuel Engelhorn, PhD.

The study was supported by the National Institutes of Health, Swim Across America, Mr. And Mrs. Quentin J. Kennedy Fund, Bioject, Inc. and Merial Ltd.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide.

The Animal Medical Center, a not-for profit veterinary hospital open 24-hours a day every day of the year, specializes in more than 20 areas of medicine and surgery. It is dedicated to providing the highest quality medical care to each one of over 60,000 patient cases seen each year. AMC has served the community in the areas of pet health care, postgraduate education of veterinarians, and clinical investigation of naturally occurring disease in animals.

Memorial Sloan Kettering Cancer Center

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