Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma.
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.
Liao
Jack C F
JC
Flaherty Comparative Oncology Laboratory, Donaldson-Atwood Cancer Clinic, The Animal Medical Center, New York, NY 10021, USA.
Gregor
Polly
P
Wolchok
Jedd D
JD
Orlandi
Francesca
F
Craft
Diane
D
Leung
Carrie
C
Houghton
Alan N
AN
Bergman
Philip J
PJ
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
D000906:Antibodies; D015478:Antigens, Heterophile; D001323:Autoantibodies; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D014442:Monophenol Monooxygenase