Abstract
Efficient expansion of hematopoietic progenitor cells requires, at least, the simultaneous stimulation of the receptors c-kit and gp130. While c-kit is activated by SCF; gp130, in cells which do not express sufficient amounts of IL-6R, can be activated by the complex of soluble IL-6R (sIL-6R) and IL-6. The therapeutic use of IL-6/sIL-6R, however, has been hampered by the high concentrations of the sIL-6R protein required. We have designed a fusion protein of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to high levels. On gp130 expressing cells the fusion protein turned out to be fully active at 100 to 1,000-fold lower concentration than the combination of unlinked IL-6 and IL-6R. The fusion protein was used to effectively expand human hematopoietic progenitor cells ex vivo in a dose dependent fashion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antigens, CD / analysis
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Antigens, CD / biosynthesis
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Antigens, CD / chemistry*
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Antigens, CD / physiology
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Antigens, CD34 / analysis
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Carcinoma, Hepatocellular
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Cell Division / drug effects*
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Cells, Cultured
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Colony-Forming Units Assay
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Cytokines / biosynthesis
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Cytokines / chemistry*
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Cytokines / pharmacology
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Drug Design
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects
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Humans
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Interleukin-6 / biosynthesis
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Interleukin-6 / chemistry*
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Interleukin-6 / pharmacology
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Liver Neoplasms
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Models, Structural
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Protein Structure, Secondary*
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin / chemistry*
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Receptors, Interleukin / physiology
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Receptors, Interleukin-6
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / chemistry*
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Recombinant Fusion Proteins / pharmacology
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Tumor Cells, Cultured
Substances
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Antigens, CD
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Antigens, CD34
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Cytokines
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Interleukin-6
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Receptors, Interleukin
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Receptors, Interleukin-6
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Recombinant Fusion Proteins
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interleukin 6-interleukin 6 receptor fusion protein, recombinant