Donor treatment with a multipegylated G-CSF maximizes graft-versus-leukemia effects

Donor treatment with granulocyle-colony stimulating factor (G-CSF) is known to modulate immune function, characterized by the generation of regulatory myelogenous and T cell populations and Th2 differentiation. Recently, these effects have been shown to be enhanced by pegylation of the G-CSF molecule, which also improves graft-versus-leukemia (GVL) via activation of invariant natural killer (iNK) T cells. We have compared G-CSF bound to a single PEG molecule (monopeg-G-CSF) as used clinically to a G-CSF molecule bound to multiple PEG molecules (multipeg-G-CSF) in major histocompatibility complex (MHC) disparate and matched models of graft-versus-host disease (GVHD) and GVL. We demonstrate that multipeg-G-CSF induces greater levels of progenitor cell, myelogenous, and iNKT cell expansion than monopeg-G-CSF, while inducing similar protection from GVHD. Despite this, multipeg-G-CSF enhanced CTL function in vivo and improved iNKT cell-dependent leukemia clearance. Thus, GVL and GVHD can be further separated after allogeneic stem cell transplantation by mobilization with a multiple-pegylated G-CSF molecule.