Augmentation of antitumor efficacy by the combination of actinomycin D with tumor necrosis factor-alpha and interferon-gamma on a melanoma model in mice

Witold Lasek, Anna Wańkowicz, Katarzyna Kuc, Wojciech Feleszko, Adam Giermasz, Marek Jakóbisiak

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The efficacy of combination treatment with actinomycin D (Act D), recombinant human tumor necrosis factor-α (TNF-α), and recombinant murine interferon-γ (IFN-γ) was examined on established MmB16 melanoma in mice. TNF-α alone had marginal effect in vitro on melanoma cells. However, when this cytokine was combined with either Act D or IFN-γ, synergistic cytostatic/cytotoxic effects were observed. The highest cytotoxicity was demonstrated in cultures of melanoma cells in which all three agents together were added. In mice inoculated with 106 melanoma cells (into the footpad of the hind limb) and treated locally with Act D, TNF-α and IFN-γ, beneficial therapeutic effects were found. When initiated 1 week after tumor cell inoculation, the 7-day treatment with all these agents administered together at daily doses: 0.2 μg (Act D), 1 μg (TNF-α), and 200 U (IFN-γ) resulted in a significant delay of tumor progression in comparison to the therapy that included either Act D alone or TNF-α in combination with IFN-γ. Side effects of such a treatment, both local and systemic, were negligible. The results of this study demonstrate that combination of regional chemotherapy (actinomycin D) and immunotherapy (TNF-α/IFN-γ) may display higher efficacy than either treatment alone and may increase therapeutic index without augmenting toxic effects.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalOncology
Volume53
Issue number1
StatePublished - Jan 1996
Externally publishedYes

Keywords

  • Actinomycin D
  • Interferon-gamma
  • Melanoma
  • Mouse model
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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