Cancer Immunity 6:8 (2006)

Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma

Jack C. F. Liao¹, Polly Gregor^2,3, Jedd D. Wolchok², Francesca Orlandi², Diane Craft¹, Carrie Leung¹, Alan N. Houghton², and Philip J. Bergman¹

¹Flaherty Comparative Oncology Laboratory, Donaldson-Atwood Cancer Clinic, The Animal Medical Center, 510 East 62nd Street, New York, NY 10021, USA
²Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
³Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Keywords: dogs, melanoma, DNA vaccine, xenogeneic, humoral immunity

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.