Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Lembcke, Luis M.; Kania, Stephen A.; Blackford, James T.; Trent, Dianne J.; Odoi, Agricola; Grosenbaugh, Deborah A.; Fraser, Darrilyn G.; Leard, Timothy; Phillips, Jeffrey

doi:10.1016/j.jevs.2012.02.011

Cited by 22 publications

(17 citation statements)

References 35 publications

(60 reference statements)

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“…The high variability of secreted cytokine amounts is paralleled by previous reports in men (Wong et al, 2008;Tarrant, 2010) and horses (Hamza et al, 2010;Lavoie-Lamoureux et al, 2012b;Lembcke et al, 2012) on spontaneous and stimulated cytokine releases. This indicates that individual animals, although clinically healthy, show up with a different baseline activation or priming of circulating cells.…”

Section: Variances Of Leukocyte Properties In Healthy Horsessupporting

confidence: 62%

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Schnabel

Steinig

Schuberth

et al. 2015

Veterinary Immunology and Immunopathology

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Section: Variances Of Leukocyte Properties In Healthy Horsessupporting

confidence: 62%

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Schnabel

Steinig

Schuberth

et al. 2015

Veterinary Immunology and Immunopathology

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“…Lembcke et al [ 17 ] vaccinated healthy horses four times with human tyrosinase DNA every two weeks, resulting in the successful induction of specific antibodies and IFNγ producing cells. They stated that the altered immunologic status of tumor-bearing patients (tumor tolerance) might make it more challenging to induce a specific immune response to tumor antigens than in healthy animals [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…No specific humoral response could be observed in the present study. In future studies additional tests to evaluate the cellular immune response [ 17 ] might give additional information about immunological mechanisms. However, in contrast to studies by Lembcke et al [ 17 ] and Phillips et al [ 37 ], we treated melanoma-bearing horses which might have developed an immune tolerance to gp100 and tyrosinase previously.…”

Section: Discussionmentioning

confidence: 99%

Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma

et al. 2015

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BackgroundEquine melanoma has a high incidence in grey horses. Xenogenic DNA vaccination may represent a promising therapeutic approach against equine melanoma as it successfully induced an immunological response in other species suffering from melanoma and in healthy horses. In a clinical study, twenty-seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9) and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, and one selected melanoma was locally treated by intradermal peritumoral injection. Prior to each injection and on day 120, the sizes of up to nine melanoma lesions per horse were measured by caliper and ultrasound. Specific serum antibodies against hgp100 and htyr were measured using cell based flow-cytometric assays. An Analysis of Variance (ANOVA) for repeated measurements was performed to identify statistically significant influences on the relative tumor volume. For post-hoc testing a Tukey-Kramer Multiple-Comparison Test was performed to compare the relative volumes on the different examination days. An ANOVA for repeated measurements was performed to analyse changes in body temperature over time. A one-way ANOVA was used to evaluate differences in body temperature between the groups. A p–value < 0.05 was considered significant for all statistical tests applied.ResultsIn all groups, the relative tumor volume decreased significantly to 79.1 ± 26.91% by day 120 (p < 0.0001, Tukey-Kramer Multiple-Comparison Test). Affiliation to treatment group, local treatment and examination modality had no significant influence on the results (ANOVA for repeated measurements). Neither a cellular nor a humoral immune response directed against htyr or hgp100 was detected. Horses had an increased body temperature on the day after vaccination.ConclusionsThis is the first clinical report on a systemic effect against equine melanoma following treatment with DNA vectors encoding eqIL12 and eqIL18 and formulated with a transfection reagent. Addition of DNA vectors encoding hgp100 respectively htyr did not potentiate this effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0422-9) contains supplementary material, which is available to authorized users.

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“…In contrast, the dogs in our study had spontaneous malignant melanoma and were of various age, gender, breed and stage of disease, thus more faithfully recapitulating the human condition. Although not formally investigated, our data and those of others, suggest a lack of correlation between pDNA dose and body weight or size (Lembcke et al .; Bergman et al . ; Liao et al .…”

Section: Discussionmentioning

confidence: 42%

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

Zuleger

Kang

Ranheim

et al. 2017

Veterinary Medicine & Sci

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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.

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Development of Immunologic Assays to Measure Response in Horses Vaccinated with Xenogeneic Plasmid DNA Encoding Human Tyrosinase

Cited by 22 publications

References 35 publications

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma

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

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