title: Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma.
abstract: Antitumor immune responses can be elicited in preclinical mouse melanoma models using plasmid DNA vaccines encoding xenogeneic melanosomal differentiation antigens. We previously reported on a phase I clinical trial of human tyrosinase (huTyr) DNA vaccination of 9 dogs with advanced malignant melanoma (World Health Organization stages II-IV), in which we demonstrated the safety of the treatment and the prolongation of the expected survival time (ST) of subjects as compared to historical, stage-matched controls. As a secondary goal of the same study, we report here on the induction of tyrosinase-specific antibody responses in three of the nine dogs vaccinated with huTyr DNA. The antibodies in two of the three responders cross-react with syngeneic canine tyrosinase, demonstrating the ability of this vaccine to overcome host immune tolerance and/or ignorance to or of "self" antigens. Most interestingly, the onset of antibody induction in these three dogs coincides with observed clinical responses and may suggest a means to account for their long-term tumor control and survival.
authors.affiliation: Flaherty Comparative Oncology Laboratory, Donaldson-Atwood Cancer Clinic, The Animal Medical Center, New York, NY 10021, USA.
authors.forename: Jack C F
authors.initials: JC
authors.lastname: Liao
authors.forename: Polly
authors.initials: P
authors.lastname: Gregor
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Francesca
authors.initials: F
authors.lastname: Orlandi
authors.forename: Diane
authors.initials: D
authors.lastname: Craft
authors.forename: Carrie
authors.initials: C
authors.lastname: Leung
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bergman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood*; D015478:Antigens, Heterophile / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D004283:Dog Diseases / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000906:Antibodies; D015478:Antigens, Heterophile; D001323:Autoantibodies; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D014442:Monophenol Monooxygenase