Mammalian cell production and purification of progenipoietin, a dual-agonist chimaeric haematopoietic growth factor

Biotechnol Appl Biochem. 2003 Feb;37(Pt 1):31-8. doi: 10.1042/ba20020046.

Abstract

One member of the progenipoietin (ProGP) family of engineered proteins, ProGP-2, is a chimaeric dual cytokine receptor agonist, expressed in mammalian cells, that stimulates both human fetal liver tyrosine kinase-3 (Flt3) and the granulocyte-colony-stimulating-factor (G-CSF) receptor. The production of ProGP-2 on a small and large scale using either anti-(Flt3 ligand) antibody-affinity chromatography, or a combination of (NH4)2SO4 fractionation, anion-exchange chromatography, hydrophobic-interaction chromatography and preparative reverse-phase chromatography is described. ProGP-2 was produced in hollow-fibre reactors containing stably transfected NS0 cells. The productivity of ProGP-2 was initially high, but was found to decrease 3-4-fold over time. When the yield of ProGP-2 decreased, the combination of three conventional chromatography steps was required to meet protein purity similar to that achieved by the anti-(Flt3 ligand) chromatography method. In addition, a protease activity was observed in conditioned media from the hollow-fibre reactors that resulted in increased degradation of ProGP-2 that was removed by hydrophobic-interaction chromatography at higher pH. Together the results demonstrated a method for production and purification of ProGP-2 for additional studies on its haematopoietic activity.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Bioreactors*
  • Cells, Cultured
  • Chromatography / methods*
  • Cloning, Molecular
  • Colony-Stimulating Factors / chemistry
  • Colony-Stimulating Factors / genetics
  • Colony-Stimulating Factors / isolation & purification*
  • Cricetinae
  • Protein Engineering / methods*
  • Quality Control
  • Receptors, Granulocyte Colony-Stimulating Factor / agonists
  • Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis
  • Receptors, Granulocyte Colony-Stimulating Factor / chemistry
  • Receptors, Granulocyte Colony-Stimulating Factor / isolation & purification
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification

Substances

  • Colony-Stimulating Factors
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Recombinant Proteins