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Home / Equine Research Bank / J Immunother / Double-blind placebo-controlled study with interleukin-18 an...
Journal of immunotherapy (Hagerstown, Md. : 1997)2010; 34(1); 58-64; doi: 10.1097/CJI.0b013e3181fe1997

Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses.

Abstract: Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, or empty plasmid DNA (control group), injected intratumorally, respectively. Tumor response was assessed using ultrasound and caliper measurements and histologic assessment of tumor biopsies. Significant tumor regression could be shown in both the treatment groups receiving IL-18 and IL-12-encoding plasmid DNA whereas placebo-treated control patients showed tumor growth over the course of the treatment. In addition, 7 of 10 tumors from horses treated with IL-18 or IL-12 showed peritumoral and/or intratumoral inflammatory infiltrates after treatment compared with 1 of the 6 in the control group. The treatment as assessed by serial blood draws and clinical investigation, was safe and well tolerated. These data suggest that the intratumoral treatment with IL-18 and IL-12-encoding plasmid DNA has antitumor effects, which is well tolerated and thus holds promise for the treatment of patients with metastatic melanoma.
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Publication Date: 2010-12-15 PubMed ID: 21150713DOI: 10.1097/CJI.0b013e3181fe1997Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the use of gene therapy, specifically interleukin-18 and interleukin-12 encoding plasmid DNA, for treating metastatic melanoma in gray horses, revealing significant tumor regression and immunologic benefits.

Research Context

  • The research focuses on melanoma, a significantly prevalent disease in gray horses. This deadly disease often progresses to a metastatic or advanced stage with limited options for effective treatment.
  • The researchers conducted a double-blind, placebo-controlled study with the aim of exploring new treatment solutions using cytokine-encoding plasmid DNA. These are injected into the tumors to trigger immunologic antitumor effects.

Research Methodology

  • The randomized study involved 26 adult gray horses suffering from metastatic melanoma. These horses formed the test subjects for the proposed gene therapy treatments using interleukin-18-encoding plasmid DNA and interleukin-12-encoding plasmid DNA.
  • The horses were divided into separate groups; each received different treatments- interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, and empty plasmid DNA (control group). These treatments were injected directly into the tumors.
  • The response of the tumors to the treatments was evaluated using ultrasound and caliper measurements, as well as through histologic examination of tumor biopsies.

Research Findings

  • The study established that a significant reduction in tumor size occurred in the groups that received the interleukin-18-encoding and interleukin-12-encoding plasmid DNA treatments. However, the control group that was given placebo showed tumor growth continuing over the course of treatment.
  • Furthermore, in terms of inflammatory infiltrates (a sign of the body’s immune response against the tumor), 7 out of 10 tumors in horses treated with either interleukin-18 or interleukin-12 showed signs of peritumoral and/or intratumoral inflammatory infiltrates, compared to just 1 out of six in the control group.
  • The treatments were assessed to be safe and well-tolerated by the horses as seen from serial blood draws and clinical investigation.

Conclusion

  • The research concludes that the intratumoral application of interleukin-18 and interleukin-12-encoding plasmid DNA has antitumor effects, triggering positive immune responses against metastatic melanoma.
  • This treatment methodology was also confirmed as safe and well-tolerated by the test subjects, marking it as a promising therapeutic strategy for patients with metastatic melanoma.

Cite This Article

APA
Müller J, Feige K, Wunderlin P, Hödl A, Meli ML, Seltenhammer M, Grest P, Nicolson L, Schelling C, Heinzerling LM. (2010). Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses. J Immunother, 34(1), 58-64. https://doi.org/10.1097/CJI.0b013e3181fe1997

Publication

Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
NlmUniqueID: 9706083
Country: United States
Language: English
Volume: 34
Issue: 1
Pages: 58-64

Researcher Affiliations

Müller, Jessika- M V
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Feige, Karsten
    Wunderlin, Patrizia
      Hödl, Andreas
        Meli, Marina L
          Seltenhammer, Monika
            Grest, Paula
              Nicolson, Lesley
                Schelling, Claude
                  Heinzerling, Lucie M

                    MeSH Terms

                    • Animals
                    • Cell Line, Tumor
                    • DNA / genetics
                    • Double-Blind Method
                    • Female
                    • Genetic Therapy
                    • Horse Diseases / therapy
                    • Horses
                    • Interleukin-12 / genetics
                    • Interleukin-12 / immunology
                    • Interleukin-18 / genetics
                    • Interleukin-18 / immunology
                    • Male
                    • Melanoma / secondary
                    • Melanoma / therapy
                    • Melanoma / veterinary
                    • Neoplasm Metastasis
                    • Placebos
                    • Plasmids

                    Citations

                    This article has been cited 21 times.
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