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Mobilization of early hematopoietic progenitor cells with BB-10010: a
genetically engineered variant of human macrophage inflammatory protein- 1
alpha
BI Lord, LB Woolford, LM Wood, LG Czaplewski, M McCourt, MG Hunter and RM Edwards
CRC Department of Experimental Haematology, Paterson Institute for Cancer
Research, Christie Hospital NHS Trust, Withington, Manchester, UK.
BB-10010 is a genetically engineered variant of human macrophage
inflammatory protein-1 alpha with improved solution properties. We show
here that it mobilizes stem cells into the peripheral blood. We
investigated the mobilizing effects of BB-10010 on the numbers of
circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and
progenitors with marrow repopulating ability (MRA). A single subcutaneous
dose of BB-10010 caused a twofold increase in circulating numbers of
CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the
effects of granulocyte colony-stimulating factor (G- CSF) and the
combination of G-CSF with BB-10010 on progenitor mobilization. Two days of
G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors
by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2
days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even
further to 38-, 33-, and 100- fold. Splenectomy resulted in increased
circulating progenitor numbers but did not change the pattern of
mobilization. Two days of treatment with G-CSF then increased circulating
CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010
administration after G-CSF treatment further increased them to 85-, 117-,
and 140-fold, respectively, compared with control. We conclude that
BB-10010 causes a rapid increase in the number of circulating hematopoietic
progenitors and further enhances the numbers induced by pretreatment with
G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors
with marrow repopulating activity, releasing four times the number achieved
with G-CSF alone. Translated into a clinical setting, this improvement in
progenitor cell mobilization may enhance the efficiency of harvest and the
quality of grafts for peripheral blood stem cell transplantation.
Volume 85,
Issue 12,
pp. 3412-3415,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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