Xenogenic human tyrosinase DNA vaccine in dogs with CMM

Abstract

Canine malignant melanoma is a common diagnosis for older dogs which can occur oral, digital or cutaneous. It has a poor prognosis because it is extremely malignant because of high growth rates and local invasiveness. Tumor excision only is no cure and chemotherapeutics are not effective. Allthough surgery and radiation therapy improves median survival times, death usually follows due to systemic metastases. The Xenogenic human tyrosinase DNA vaccination therapy gives a humoral and cellular response by interfering with antigens involved in melanoma differentiation. Muscle cells in which the vaccine is administrated take up tyrosinase antigen which is expressed on the cell surface. This is recognized by antigen presenting cells which migrate to draining lymph nodes. This gives an induction of antibody and T-cell response which lysate the tumor cells. The vaccine encodes human tyrosinase by a xenogenic plasmid DNA with a cDNA insert. Now a tyrosinase protein is produced which is homologous to canine tyrosinase, but varies enough to induce an immune response. The tyrosinase specific antibodies cross-react with canine tyrosinase. Now the tyrosinase antigen is transcribed and translated in the canine host which is recognized by its relevant MHC. As opposed to normal melanocytes, malignant melanocytes express class II MHC molecules which present antigen on the melanoma cell surface which then give an immune response towards the tumor. To determine if the Xenogenic human tyrosinase DNA treatment is effective and has improved survival times compared to previously published data on canine malignant melanoma treatment results, the RFI, MFI, DFI and ST were determined. A total group of 32 dogs with CMM were followed over a total course of three years. We found that patients with a more progressed melanoma tumor and/or metastases had a shorter survival time and a higher risk of dying. Tumors that were not or incompletely removed had a higher risk of resulting into death of the patient and gave lower survival times. Patients with CMM treated with the vaccine and conventional therapies had much longer survival times than dogs with CMM only treated with conventional therapies. The quality of life of the patients was determined by a questionnaire and the RFI, which was two times longer than in previous studies, which may indicate that the vaccine improves the quality of life of a patient with CMM.