Canine Malignant Melanoma: Surgery and Vaccination (DNA Vaccine & an ltalian Alternative)

Introduction
Immunogenicity of malignant melanoma (MM) has stimulated interest in the development of cancer vaccines. Canine (c) malignant melanoma (MM) shares many characteristics with human MM (histology, tumor genetics, clinical behavior). cMM thus representing an attractive translational model for the assessment of the efficacy of novel immunotherapeutic treatments, also in a comparative setting.

A suitable immunotherapeutic target should have a strong role in tumor development and progression, be expressed in malignant cells in a high percentage of patients, and show limited distribution in normal tissues. Chondroitin sulfate proteoglycan-4 (CSPG4), an early cell surface progression marker involved in tumor cell proliferation, migration and invasion meets these criteria. CSPG4 is highly conserved in its structural and functional properties through phylogenetic evolution. In particular, human (h) CSPG4 displays 82% homology and 88% similarity to its canine counterpart in its amino-acidic sequence. Moreover, the frequency of CSPG4 expression in canine and human melanoma lesions is quite similar, being about 60% and 80%, respectively. The introduction of electroporation to DNA vaccine delivery (electrovaccination) has strongly increased immunogenicity and therapeutic efficacy in both mice and humans. Electrovaccination combines the advantages of DNA vaccination and electroporation, the latter enhancing the expression of the protein encoded by the immunizing DNA and prolonging the duration of the immune response.

So far adjuvant chemotherapy has failed to prolong survival in surgically resected MM dogs. Therefore we decided to test both safety and efficacy of intramuscular electrovaccination of a plasmid encoding for CSPG4 in client-owned dogs with surgically resected stage II-III CSPG4-positive, natural occurring oral MM. Since CSPG4 is a self-antigen with poor or none immunogenicity in autologous hosts, we immunized dogs with hCSPG4.  [...]