Open AccessPilot study of safety and feasibility of DNA microseeding for treatment of spontaneous canine melanoma
Author(s) -
Zuleger Cindy L.,
Kang Chulhi,
Ranheim Erik A.,
Kurzman Ilene D.,
Macklin Michael D.,
Newton Michael A.,
Wolchok Jedd D.,
Vail David M.,
Eriksson Elof,
Albertini Mark R.
Publication year - 2017
Publication title -
veterinary medicine and science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.485
H-Index - 11
ISSN - 2053-1095
DOI - 10.1002/vms3.65
Subject(s) - melanoma , medicine , immunogenicity , dna vaccination , immunotherapy , naked dna , immunology , immune system , dna , cancer research , immunization , biology , plasmid , genetics
Spontaneous canine malignant melanoma provides an excellent pre‐clinical model to study DNA vaccines for melanoma immunotherapy. A USDA ‐approved xenogeneic human tyrosinase (hu TYR ) 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 hu TYR 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‐hu TYR ELISA was used to test pre‐ and post‐treatment sera. Biopsies of treated skin were obtained for detection of hu TYR transgene expression. DNA microseeding was well tolerated with no significant toxicity detected beyond local site irritation, and there were no signs of autoimmunity. hu TYR ‐expressing cells were observed in biopsies of hu TYR DNA microseeding sites. Increased humoral anti‐hu TYR 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.