| 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. © 2006 by Philip J. Bergman. |
