EGF-IL-18 fusion protein as a potential anti-tumor reagent by induction of immune response and apoptosis in cancer cells

Cancer Lett. 2008 Feb 18;260(1-2):187-97. doi: 10.1016/j.canlet.2007.10.042. Epub 2007 Dec 21.

Abstract

We report here the generation and characterization of EGF-IL-18 fusion protein as an anti-tumor reagent. The epidermal growth factor (EGF) and interleukin-18 (IL-18) fusion protein was shown to induce interferon-gamma (IFNgamma) expression and secretion in KG-1 cells, and to promote PBMNC proliferation. It also stimulated activation of CD4+ T cells, and increased other immune responses. Moreover, EGF-IL-18 could induce significant tumor regression in SMMC-7721-xenografted Balb/c nude mice when administered together with peritumoral injection of X-ray-irradiated NK-92 cells, and this regression is associated with arresting of the tumor cells in G1 phase and induction of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / enzymology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism
  • Female
  • G1 Phase
  • Humans
  • Immune System / drug effects*
  • Immune System / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Interferon-gamma / metabolism
  • Interleukin-18 / pharmacology*
  • Interleukin-18 / therapeutic use
  • K562 Cells
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / radiation effects
  • Leukocytes, Mononuclear / drug effects
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Time Factors
  • Viral Fusion Proteins / pharmacology*
  • Viral Fusion Proteins / therapeutic use
  • X-Rays
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • EGF-IL-18 fusion protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-18
  • Peptides
  • Viral Fusion Proteins
  • vaccinia growth factor
  • Interferon-gamma
  • ErbB Receptors