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Journal of molecular medicine (Berlin, Germany)2001; 78(12); 692-702; doi: 10.1007/s001090000165

Tumor regression induced by intratumoral injection of DNA coding for human interleukin 12 into melanoma metastases in gray horses.

Abstract: Preclinical studies investigating new therapeutic principles against melanoma are presently being carried out in mouse models; however, these are not optimal. Here we describe a novel animal model using gray horses. These animals spontaneously develop metastatic melanoma that resembles human disease and is thus highly relevant for preclinical studies testing new immunotherapy protocols. We found that injection of plasmid DNA coding for the human cytokine interleukin 12 into established metastases induced significant regression in all 12 treated lesions in a total of 7 horses. Complete disappearance was observed in one treated lesion, with no recurrence after 6 months. No adverse events have been observed in any of the animals during and after treatment. These results demonstrate the effectiveness and safety of interleukin 12 encoding plasmid DNA therapy against established metastatic disease in a large animal model and serve as a basis for a clinical trial.
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Publication Date: 2001-07-04 PubMed ID: 11434722DOI: 10.1007/s001090000165Google Scholar: Lookup
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  • Journal Article

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.

This research used gray horses, which naturally develop melanoma similar to that in humans, to test a new immunotherapy treatment for metastatic melanoma. The research found that injecting the gene coding for the human protein interleukin 12 into existing melanoma tumors caused significant shrinkage, and in one horse the tumor disappeared entirely without recurring.

Study Overview

The scientists conducted preclinical studies to explore new therapeutic principles to combat melanoma using a novel animal model: gray horses. Gray horses were used because they develop metastatic melanoma like human disease and therefore present a highly relevant model for the testing of new immunotherapy protocols.

Immunotherapy Protocols

  • Scientists tested a method involving the injection of plasmid DNA that codes for the human cytokine interleukin 12 into established metastases.
  • Interleukin 12 is a cytokine, a type of signaling molecule in the immune system that helps coordinate the body’s response to infections and diseases. It has been linked to the body’s ability to fight off cancer.
  • Through this method, the intention was to stimulate the immune system of the horse to recognize and destroy the melanoma cells.

Results

  • Injection of the plasmid DNA led to significant regression in all 12 treated melanoma lesions across seven horses.
  • In one treated lesion, complete disappearance was observed, and importantly, there was no recurrence of the tumor after 6 months.
  • No adverse events or side effects were observed in any of the horses during and after treatment, which suggested that the studied immunotherapy protocol was safe and well-tolerated.

Implications of Research

  • This research provides a strong case for the effectiveness and safety of interleukin 12 encoding plasmid DNA therapy in treating established metastatic disease, at least in a large animal model.
  • The results from this research set the stage for the potential initiation of a clinical trial testing the use of interleukin 12 encoding plasmid DNA therapy for melanoma treatment in humans.

Cite This Article

APA
Heinzerling LM, Feige K, Rieder S, Akens MK, Dummer R, Stranzinger G, Moelling K. (2001). Tumor regression induced by intratumoral injection of DNA coding for human interleukin 12 into melanoma metastases in gray horses. J Mol Med (Berl), 78(12), 692-702. https://doi.org/10.1007/s001090000165

Publication

Journal of molecular medicine (Berlin, Germany)
ISSN: 0946-2716
NlmUniqueID: 9504370
Country: Germany
Language: English
Volume: 78
Issue: 12
Pages: 692-702

Researcher Affiliations

Heinzerling, L M
  • Institute of Medical Virology, University of Zurich, Switzerland.
Feige, K
    Rieder, S
      Akens, M K
        Dummer, R
          Stranzinger, G
            Moelling, K

              MeSH Terms

              • Aging
              • Animals
              • Cell Division
              • Disease Models, Animal
              • Female
              • Genetic Therapy
              • Horses / genetics
              • Humans
              • Immunohistochemistry
              • Immunotherapy
              • Interferon-gamma / genetics
              • Interleukin-12 / adverse effects
              • Interleukin-12 / genetics
              • Interleukin-12 / immunology
              • Interleukin-12 / therapeutic use
              • Male
              • Melanoma / genetics
              • Melanoma / immunology
              • Melanoma / pathology
              • Melanoma / therapy
              • Neoplasm Metastasis / genetics
              • Neoplasm Metastasis / immunology
              • Neoplasm Metastasis / pathology
              • Neoplasm Metastasis / therapy
              • Plasmids / administration & dosage
              • Plasmids / adverse effects
              • Plasmids / genetics
              • RNA, Messenger / genetics
              • RNA, Messenger / metabolism
              • Treatment Outcome
              • Tumor Cells, Cultured

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