Autologous Dendritic Cell Vaccination of Dogs with Oral Melanoma Using Human GP100 Antigen
Melanoma, the most common oropharyngeal cancer in dogs, is characterized by local invasion and early widespread metastases. Surgery and/or radiation therapy have been employed for local control; however, chemotherapy has not been successful at preventing systemic metastatic disease. Therefore, immunotherapy in the form of vaccines is being investigated for control of metastatic disease. Recent advances cloning tumour associated antigens (e.g., gp100) which are potential immunological targets and adoptive gene transfer techniques have led to new novel approaches to cancer therapy. The purpose of this prospective study was to assess the use of autologous dendritic cell vaccination using xenogenic human gp100 antigen for the treatment of canine oral melanoma.
Dogs presenting to the Veterinary Teaching Hospital of the Ontario Veterinary College with histologically confirmed oral melanoma and staging were entered into the study. Staging consisted of primary tumour size, mandibular lymph node aspirate or biopsy, and 3-view thoracic radiographs. Local disease was controlled by surgery or radiation. Dendritic cells were harvested (initially from bone marrow and later from peripheral blood), expanded ex vivo, transduced with a vector expressing a human xenoantigen (Ad-5-hgp100), and then vaccinated intradermally (3 vaccines q monthly).
Eleven dogs were entered consisting of 10 female (spayed), 1 male (neutered); mean and median age 10 years (range 4 to 17 years); various breeds, with WHO stage I (3 dogs), II (1 dog), and III (7 dogs). The overall median survival was 439 days (mean 613; range 130-2,204 days). By WHO stage the median survival was stage I (425 days), II (130 days), and III (439 days). No toxicity was observed in any of the dogs receiving the vaccines.
This study demonstrated the feasibility and safety of culturing canine dendritic cells and then transducing the dendritic cells with an adenovirus expressing a xenogenic tumour antigen for vaccinating dogs. Further studies will be needed to determine the efficacy of this immunotherapeutic approach for the treatment of oral melanoma in dogs.