title: CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA.
abstract: OBJECTIVE
  Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.
  
  
  METHODS
  Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.
  
  
  RESULTS
  hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response.
  
  
  CONCLUSIONS
  Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino;
authors.forename: Federica
authors.initials: F
authors.lastname: Riccardo
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Selina
authors.initials: S
authors.lastname: Iussich
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Lorella
authors.initials: L
authors.lastname: Maniscalco
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Saray
authors.initials: S
authors.lastname: Lorda Mayayo
authors.affiliation: Veterinary practitioner; and.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Rosa
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino;
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Raffaella
authors.initials: R
authors.lastname: De Maria
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Gattino
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino;
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Elena
authors.initials: E
authors.lastname: Lardone
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Marina
authors.initials: M
authors.lastname: Martano
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morello
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino;
authors.forename: Simone
authors.initials: S
authors.lastname: Prestigio
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino;
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fiore
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino;
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy;
authors.forename: Sara
authors.initials: S
authors.lastname: Zabarino
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.affiliation: Department of Veterinary Science, University of Torino, Grugliasco, Torino, Italy; federica.cavallo@unito.it paolo.buracco@unito.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Buracco
authors.affiliation: Authors' Affiliations: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino; federica.cavallo@unito.it paolo.buracco@unito.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D011508:Chondroitin Sulfate Proteoglycans / Q000276:immunology / Q000378:metabolism; D018572:Disease-Free Survival; D004283:Dog Diseases / Q000401:mortality / Q000628:therapy*; D004285:Dogs; D053672:Electrochemotherapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000628:therapy / Q000662:veterinary*; D008546:Melanoma, Experimental; D009062:Mouth Neoplasms / Q000401:mortality / Q000628:therapy / Q000662:veterinary*
chemical_list: D019496:Cancer Vaccines; D011508:Chondroitin Sulfate Proteoglycans