title: Donor treatment with a multipegylated G-CSF maximizes graft-versus-leukemia effects.
abstract: 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.
authors.affiliation: The Queensland Institute of Medical Research, 300 Herston Road, QLD 4006, Australia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Banovic
authors.forename: Kelli P A
authors.initials: KP
authors.lastname: MacDonald
authors.forename: Kate A
authors.initials: KA
authors.lastname: Markey
authors.forename: Edward S
authors.initials: ES
authors.lastname: Morris
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Kuns
authors.forename: Antiopi
authors.initials: A
authors.lastname: Varelias
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
mesh_terms: D000818:Animals; D006086:Graft vs Host Disease / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D007942:Leukemia, Experimental / Q000628:therapy; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols