Oral melanoma: Improving dogs' survival

It is not often that one is able to bear witness to a sea change. The veterinary community has, in my opinion, seen one with the development of the melanoma vaccine. This unique form of therapy, a DNA-based vaccine, would justify my opinion, but the successful collaboration between veterinary oncologists, human oncologists and the pharmaceutical industry also serve to mark this event as extraordinary.

Oral melanoma is the most common malignant tumor of the oral cavity in dogs. These animals typically present for malodorous breath, oral bleeding, a change in mastication or food preference (hard to soft foods) or the finding of a mass on oral examination. These tumors can be pigmented but may appear as fleshy and non-pigmented.

This tumor typically has a very aggressive biologic behavior with a high metastatic rate to the regional lymph nodes and lungs. Palpation should be performed and a fine needle aspirate of the draining lymph nodes should be obtained for cytologic analysis.

Lymph nodes affected by metastatic melanoma may not feel enlarged or firmer than normal yet still show evidence of metastatic melanoma via fine-needle aspiration or histopathology. Chest radiographs should be obtained at the time of diagnosis to assess for pulmonary metastasis. Early melanoma metastases often are subtle, so should be evaluated very carefully.

Historically, therapy involved aggressive surgery (partial mandibulectomy or maxillectomy) with or without local radiation therapy and adjuvant chemotherapy. Even with this aggressive approach, median survival times for dogs with oral melanomas (grade II tumors > 2cm, grade III regional lymph node metastases, or grade IV — distant metastasis) were less than 150 days, the dogs typically succumbing to metastatic disease.

The melanoma vaccine is based upon the concept of xenogeneic DNA vaccination. Plasmid DNA that codes for human tyrosinase (a protein over-expressed on melanoma cells) is injected into the muscle of the dog. These muscle cells take up the DNA and start expressing it by producing the human protein.

Because the protein is the human form, the dog's immune system, both B and T cells, recognize it as foreign and mount an attack. Because this protein is similar to the dog tyrosinase, the attack targets cells that express native (canine) tyrosinase, i.e., the melanoma cells which have a very high expression of this protein.

With good local control of the oral melanomas, either surgery alone or surgery in conjunction with radiation therapy, the melanoma vaccine provides excellent systemic therapy. In dogs in which local control is achieved, the vaccine has been shown to increase median survival times in dogs with oral melanomas to over a year.

The science behind this product, xenogeneic vaccination, is fascinating. It may help in the treatment of many types of malignancies. The collaboration between human and veterinary oncologists and the pharmaceutical industry helped bring this product to market. This collaboration should serve as a model to both the scientific community and the biotech/pharmaceutical industry.

Dr. Gerald Post is one of about 180 board-certified veterinary oncologists in the United States. He graduated with honors from Cornell University and obtained his DVM degree from the University of Minnesota. He has almost two decades of clinical experience treating pets with cancer and in 1997 formed the Veterinary Oncology and Hematology Center, a highly successful private veterinary oncology practice with multiple locations in Connecticut and New York. Dr. Post started the Animal Cancer Foundation (www.acfoundation.org) in 1999 to serve as the integral link between the millions of pets with cancer and the biotechnology community. His mission is to promote cooperation leading to more effective cancer treatment in pets and more efficient and economical trial of new therapeutics that also may prove effective in treating human cancers.