A BIOACTIVE DESIGNER CYTOKINE FOR HUMAN HEMATOPOIETIC PROGENITOR-CELLEXPANSION

Efficient expansion of hematopoietic progenitor cells requires, at lea st, the simultaneous stimulation of the receptors c-kit and gp130, Whi le c-kit is activated by SCF; gp130, in cells which do not express suf ficient amounts of IL-6R, can be activated by the complex of soluble I L-6R (sIL-6R) and IL-6, The therapeutic use of IL-6/sIL-6R, however, h as been hampered by the high concentrations of the sIL-6R protein requ ired, 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 1 00 to 1,000-fold lower concentration than the combination of unlinked IL-6 and IL-6R. The fusion protein was used to effectively expand huma n hematopoietic progenitor cells ex vivo in a dose dependent fashion.