April 24, 2018
Safety and Immunoreactivity of a Xenogeneic DNA Plasmid Vaccine Expressing Human Tyrosinase in Tumor-Bearing Horses
Luis M. Lembcke2, James T. Blackford2, Deborah A. Grosenbaugh3, Timothy Leard3, Stephen A. Kania2, Dianne J. Trent2, Keith Prater2, John Biggerstaff2, Agricola Odoi2, and Jeffrey C. Phillips1. 1. Lincoln Memorial University College of Veterinary Medicine, Harrogate, TN. 2. University of Tennessee, Knoxville, TN. 3. Merial Ltd., Athens, GA.
The purpose of this study was to evaluate the safety and immunologic activity of the pING-HuTyr plasmid (Oncept™) in horses diagnosed with melanoma. This vaccine has been previously reported to be effective for treating melanoma in dogs. To accomplish our goal we proposed a study wherein the vaccine was used in gradually escalating doses in horses that had been diagnosed with melanoma while temporally measuring immunologic response in these treated patients. The protocol involved treating a total of 15 horses with a series of 4-biweekly injections along with a 6-month booster. Biologic samples were collected during the protocol to measure antibody and in vitro cellular reactivity to human tyrosinase, cellular reactivity to equine tyrosinase, and finally to characterize tumor infiltrating lymphocyte populations.
No adverse reactions have been seen in any of the vaccinated patients. Objective responses were seen in 13 of 15 treated horses. Positive humoral responses were seen in all treated horses. Cellular reactivity was noted in 13 of 15 treated patients. Characterization of tumor infiltrating lymphocyte populations identified a statistically significant increase in CD8+ lymphocytes along with a decrease in CD4+/Foxp3+ regulatory T cells following vaccination. Increasing plasmid dose did not appear to be associated with an increase in either clinical activity or immunologic reactivity. This xenogenic vaccine appears to be safe and well tolerated in tumor bearing horses and appears to result in both clinical activity and a measureable immune response in treated patients.
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