Researchers at Immunex Corp. have constructed molecules thatcombine two immune messenger proteins, and the combinationappears to work better than the components.
Both messengers, called cytokines, help control the bonemarrow's manufacture of immune cells such as granulocytesand macrophages. Yet the fused molecules of interleukin-3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) appear to be more potent stimulators of human bonemarrow than either messenger alone, the researchers report inthis month's issue of the Proceedings of the National Academyof Sciences.
"To my knowledge, this is the first approach coupling twodifferent cytokine genes in their full length," Immunexscientist Douglas E. Williams, one of the report's authors, toldBioWorld.
Clinical trials of the combination cytokine are set for thisfall, company spokesman Jason Rubin said.
Immunex, a Seattle-based company that is developing severalinterleukins as possible therapeutic agents, won marketingapproval in March for GM-CSF to treat autologous bone marrowtransplant patients suffering neutropenia, or low white bloodcell counts.
Working with scientists from the Indiana University School ofMedicine, Immunex researchers constructed genes for both anIL-3/GM-CSF molecule and a GM-CSF/IL-3 molecule andexpressed the fused genes in yeast. The flexible linking sectionallowed free movement of each messenger molecule. Each wastheoretically able to interact freely with its receptors onimmune cells.
The tenfold to twentyfold increased potency of the fused GM-CSF/IL-3 molecule could come from concerted action atreceptors on immune cells that normally receive themessengers separately, the researchers suggested. Thereceptor thus receives two hits when the combination messagearrives.
-- Roberta Friedman, Ph.D. Special to BioWorld
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