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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / enzymology
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Cell Proliferation / drug effects
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Cells, Cultured
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ErbB Receptors / drug effects
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ErbB Receptors / metabolism
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Female
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G1 Phase
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Humans
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Immune System / drug effects*
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Immune System / metabolism
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Intercellular Signaling Peptides and Proteins
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Interferon-gamma / metabolism
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Interleukin-18 / pharmacology*
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Interleukin-18 / therapeutic use
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K562 Cells
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / radiation effects
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Leukocytes, Mononuclear / drug effects
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Liver Neoplasms, Experimental / drug therapy*
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Liver Neoplasms, Experimental / immunology
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Liver Neoplasms, Experimental / metabolism
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Liver Neoplasms, Experimental / pathology
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Peptides / pharmacology*
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Peptides / therapeutic use
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Time Factors
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Viral Fusion Proteins / pharmacology*
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Viral Fusion Proteins / therapeutic use
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X-Rays
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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EGF-IL-18 fusion protein, mouse
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Intercellular Signaling Peptides and Proteins
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Interleukin-18
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Peptides
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Viral Fusion Proteins
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vaccinia growth factor
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Interferon-gamma
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ErbB Receptors