Prevention of angiogenesis by naked DNA IL-12 gene transfer: Angioprevention by immunogene therapy

M. Morini, A. Albini, G. Lorusso, K. Moelling, B. Lu, M. Cilli, S. Ferrini, D. M. Noonan

Research output: Contribution to journalArticle

Abstract

IL-12 is thought to induce a cytokine cascade with antiangiogenic effects mediated by IFN-γ and angiostatic CXCR3 chemokine ligands. Naked DNA intramuscular injection of an expression vector plasmid producing IL-12 resulted in significant, well-tolerated elevation of serum IL-12 levels. Injection of the IL-12 plasmid at least 2 days, and up to 20 days, before subcutaneous injection of matrigel with angiogenic factors resulted in strong prevention of angiogenesis in both C57/bl and nude mice. A single injection of the IL-12 plasmid contemporarily with the matrigel or 2 days after resulted in partial, statistically not significant, inhibition. Control plasmid injection did not affect either angiogenesis or angiogenesis inhibition by IL-12 protein in vivo. Angiogenesis inhibition was observed in NK cell-depleted C57/bl and nude mice as well as in IFN-γ-/- and CXCR3-/- knockout mice, indicating that NK- and/or T-cell-initiated IFN-γ- chemokine cascades were not involved in the angiogenesis inhibition observed in vivo. Finally, IL-12 plasmid DNA gene transfer significantly prevented the growth and vascularization of highly angiogenic KS-Imm Kaposi's sarcoma and TS/A murine mammary carcinoma tumors in nude and/or syngeneic mice. These data suggest that a preventive gene therapy approach using antiangiogenic cytokines can effectively inhibit tumor angiogenesis and KS, representing an example of angioimmunoprevention.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalGene Therapy
Volume11
Issue number3
DOIs
Publication statusPublished - Feb 2004

Keywords

  • Interferon gamma
  • Interleukin-12
  • Kaposi's sarcoma
  • Naked DNA
  • Tumor angiogenesis

ASJC Scopus subject areas

  • Genetics

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