Pilot study of safety and feasibility of DNA microseeding for treatment of spontaneous canine melanoma

Abstract

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.

Treatment of Canine Oral Melanomas: A Critical Review of the Literature

“…The safety and possible potentiating role of novel vaccine delivery systems, namely microseeding and electrovaccination, have also been evaluated in dogs with OMM [ 89 , 90 , 91 , 92 , 93 ]. DNA microseeding makes use of a modified tattooing device to deposit vaccine at a controlled rate into micropunctures created intradermally ( Table 10 ) [ 89 ].…”

“…The safety and possible potentiating role of novel vaccine delivery systems, namely microseeding and electrovaccination, have also been evaluated in dogs with OMM [ 89 , 90 , 91 , 92 , 93 ]. DNA microseeding makes use of a modified tattooing device to deposit vaccine at a controlled rate into micropunctures created intradermally ( Table 10 ) [ 89 ]. In a pilot study including four dogs with OMM, delivery of a xenogeneic human tyrosinase plasmid DNA vaccine via microseeding was found to be well tolerated but the study lacked sufficient power to evaluate true antitumoral effects [ 89 ].…”

The future of cancer immunotherapy: DNA vaccines leading the way

“…It is the United States Food and Drug Administration (USFDA)-approved xenogeneic human tyrosinase plasmid DNA vaccine, used to mitigate malignant melanoma in dogs. It targets a self-antigen termed tyrosinase which is upregulated in several malignant melanomas, in dogs as well as humans [ 85 ]. Furthermore, a novel technology utilizes CRISPR/Cas9 based gene-editing technology, in vaccine development.…”

Emerging Technologies for Low‐Cost, Rapid Vaccine Manufacture

“…These proxies indicate the feasibility of producing vaccines using the emerging platform technologies analysed herein. 2005 USDA IHNV surface glycoprotein G DNA [37,38] Melanoma, for canines (ONCEPT ® ) 2010 USDA human tyrosinase antigen DNA [37,39] * These vaccine expression systems and platform technologies were used as proxies for the 4 emerging technologies as follow: yeast expression system for the humanised, high-yield yeast platform; the insect cell expression system for the insect cell-baculovirus ADDomer TM vaccines; Detergent-extracted OMVs for the GMMA platform; and DNA vaccines for the RNA vaccines.…”