Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.
Abstract: Equine 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. Results: In 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. Conclusions: This 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.
Publication Date: 2015-06-11 PubMed ID: 26063232PubMed Central: PMC4464139DOI: 10.1186/s12917-015-0422-9Google Scholar: Lookup
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Summary
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The study explores the use of DNA vaccination as a solution to equine melanoma in grey horses. Vaccination was conducted using DNA vectors with different combinations, and the researchers observed how they affected tumor volume and the general response of the horse.
Research Design
- The study entailed a clinical examination of 27 grey, melanoma-bearing horses. The horses were divided into three groups of nine.
- These horses were vaccinated on three different days (1, 22, and 78) with DNA vectors. The vectors were encoded for equine IL-12 and IL-18 alone or combined with either human glycoprotein 100 or human tyrosinase.
- The vaccines were administered intramuscularly, and a selected melanoma was locally treated via an intradermal peritumoral injection.
- Prior to each injection and on day 120, the researchers measured the sizes of up to nine melanoma lesions per horse through the use of a caliper and ultrasound.
- Serum antibodies against human glycoprotein 100 and human tyrosinase were measured using cell based flow-cytometric assays.
Statistical Analysis
- An Analysis of Variance (ANOVA) for repeated measurements helped to identify significant influences on the relative tumor volume. Other variables like affiliation to treatment group, local treatment and examination modality were also considered in the ANOVA analysis.
- Tukey-Kramer Multiple-Comparison Test was used for post-hoc testing, to compare the relative volumes on the different examination days.
- Body temperature over time was also analyzed using ANOVA for repeated measurements. A one-way ANOVA was used to evaluate differences in body temperature between the groups. All p-values less than 0.05 were considered statistically significant across all tests.
Results and Conclusion
- The findings showed that the relative tumor volume dropped significantly to 79.1 ± 26.91% by day 120. Notably, analysis showed that factors like the treatment group, local treatment, and examination modality had no significant influence on the results.
- There was no cellular or humoral immune response directed against human tyrosinase or human glycoprotein 100 detected.
- Post-vaccination, horses exhibited increased body temperature on the day after vaccination.
- The study concludes that this represents the first clinical report on a systemic effect counteracting equine melanoma following treatment with DNA vectors encoded with equine IL12 and IL18 and formulated using a transfection reagent.
- Addition of DNA vectors encoding human glycoprotein 100 or human tyrosinase failed to intensify this effect. They observed that the relative tumor volume decreased, regardless of the additional vectors or local treatment.
Cite This Article
APA
Mählmann K, Feige K, Juhls C, Endmann A, Schuberth HJ, Oswald D, Hellige M, Doherr M, Cavalleri JM.
(2015).
Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.
BMC Vet Res, 11, 132.
https://doi.org/10.1186/s12917-015-0422-9 Publication
Researcher Affiliations
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany. kathrin.maehlmann@vetsuisse.unibe.ch.
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany. karsten.feige@tiho-hannover.de.
- Mologen AG, Berlin, Germany. juhls@mologen.com.
- Mologen AG, Berlin, Germany. endmann@mologen.com.
- Immunology Unit, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany. hans-joachim.schuberth@tiho-hannover.de.
- Mologen AG, Berlin, Germany. Oswald@mologen.com.
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany. maren.hellige@tiho-hannover.de.
- Institute for Veterinary Epidemiology and Biostatistics, Free University of Berlin, Berlin, Germany. marcus.doherr@fu-berlin.de.
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany. jessika.cavalleri@tiho-hannover.de.
MeSH Terms
- Animals
- CHO Cells
- Cancer Vaccines / therapeutic use
- Cricetinae
- Cricetulus
- Female
- Horse Diseases / therapy
- Horses
- Male
- Melanoma / therapy
- Melanoma / veterinary
- Pigments, Biological
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Transfection
References
This article includes 42 references
Citations
This article has been cited 4 times.- Gao W, Pan J, Pan J. Antitumor Activities of Interleukin-12 in Melanoma.. Cancers (Basel) 2022 Nov 14;14(22).
- Weber LA, Delarocque J, Feige K, Kietzmann M, Kalbitz J, Meißner J, Paschke R, Cavalleri JV. Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses.. Animals (Basel) 2021 Nov 13;11(11).
- Weber LA, Funtan A, Paschke R, Delarocque J, Kalbitz J, Meißner J, Feige K, Kietzmann M, Cavalleri JV. In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer.. PLoS One 2020;15(11):e0241448.
- Lopes A, Vandermeulen G, Préat V. Cancer DNA vaccines: current preclinical and clinical developments and future perspectives.. J Exp Clin Cancer Res 2019 Apr 5;38(1):146.
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