6533b829fe1ef96bd128ae5a
RESEARCH PRODUCT
A bioactive designer cytokine for human hematopoietic progenitor cell expansion
C. PeschelKarl-josef KallenAxel WollmerJutta GoldschmittMartina FischerStefan Rose JohnJust P. G. BrakenhoffJoachim Grötzingersubject
Carcinoma HepatocellularRecombinant Fusion Proteinsmedicine.medical_treatmentBiomedical EngineeringAntigens CD34BioengineeringBiologyApplied Microbiology and BiotechnologyProtein Structure SecondaryColony-Forming Units AssayAntigens CDTumor Cells CulturedmedicineHumansAmino Acid SequenceReceptorCells CulturedInterleukin 3Interleukin-6Cell growthLiver NeoplasmsReceptors InterleukinHematopoietic Stem CellsGlycoprotein 130Receptors Interleukin-6Fusion proteinCell biologyModels StructuralCytokineDrug DesignImmunologyCytokinesMolecular MedicineStem cellCell DivisionEx vivoBiotechnologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1997-02-01 | Nature Biotechnology |