I. A bioactive designer cytokine for human hematopoietic progenitor cell expansion

Nat Biotechnol. 1997 Feb;15(2):142-5. doi: 10.1038/nbt0297-142.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / analysis
  • Antigens, CD / biosynthesis
  • Antigens, CD / chemistry*
  • Antigens, CD / physiology
  • Antigens, CD34 / analysis
  • Carcinoma, Hepatocellular
  • Cell Division / drug effects*
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Cytokines / biosynthesis
  • Cytokines / chemistry*
  • Cytokines / pharmacology
  • Drug Design
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / chemistry*
  • Interleukin-6 / pharmacology
  • Liver Neoplasms
  • Models, Structural
  • Protein Structure, Secondary*
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / pharmacology
  • Tumor Cells, Cultured


  • Antigens, CD
  • Antigens, CD34
  • Cytokines
  • Interleukin-6
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins
  • interleukin 6-interleukin 6 receptor fusion protein, recombinant