Spontaneous canine
malignant melanoma provides an excellent pre-clinical model to study
DNA vaccines for
melanoma immunotherapy. A USDA-approved xenogeneic human
tyrosinase (huTYR) plasmid
DNA vaccine delivered intramuscularly induces detectable immune responses and has clinical activity in some dogs with
melanoma. The objective of this pilot study was to evaluate the feasibility, safety and immunogenicity of huTYR plasmid
DNA administered to the skin via microseeding in dogs with spontaneous
melanoma.
DNA microseeding utilizes a modified
tattooing device as an alternate and potentially more potent delivery method for
DNA immunization.
DNA was delivered to shaved inner thigh skin of six companion dogs with
melanoma approximately every 14 days for a planned total of four vaccination time points. An anti-huTYR ELISA was used to test pre- and post-treatment sera. Biopsies of treated skin were obtained for detection of huTYR transgene expression.
DNA microseeding was well tolerated with no significant toxicity detected beyond local site irritation, and there were no signs of autoimmunity. huTYR-expressing cells were observed in biopsies of huTYR
DNA microseeding sites. Increased humoral anti-huTYR
antibodies were seen in two of five evaluable dogs following microseeding compared to baseline.
DNA microseeding is well tolerated in companion dogs with
melanoma. Further investigation is needed to determine if combining
DNA microseeding with other
immunotherapy regimens potentiates this delivery platform for
cancer immunotherapy.