Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors
dc.contributor.author | Chua, Hui Lin | |
dc.contributor.author | Plett, P. Artur | |
dc.contributor.author | Sampson, Carol H. | |
dc.contributor.author | Katz, Barry P. | |
dc.contributor.author | Carnathan, Gilbert W. | |
dc.contributor.author | MacVittie, Thomas J. | |
dc.contributor.author | Lenden, Keith | |
dc.contributor.author | Orschell, Christie M. | |
dc.contributor.department | Department of Medicine, IU School of Medicine | en_US |
dc.date.accessioned | 2016-03-24T14:31:31Z | |
dc.date.available | 2016-03-24T14:31:31Z | |
dc.date.issued | 2014-01 | |
dc.description.abstract | In an effort to expand the worldwide pool of available medical countermeasures (MCM) against radiation, the PEGylated G-CSF (PEG-G-CSF) molecules Neulasta and Maxy-G34, a novel PEG-G-CSF designed for increased half-life and enhanced activity compared to Neulasta, were examined in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS), along with the lead MCM for licensure and stockpiling, G-CSF. Both PEG-G-CSFs were shown to retain significant survival efficacy when administered as a single dose 24 h post-exposure, compared to the 16 daily doses of G-CSF required for survival efficacy. Furthermore, 0.1 mg kg of either PEG-G-CSF affected survival of lethally-irradiated mice that was similar to a 10-fold higher dose. The one dose/low dose administration schedules are attractive attributes of radiation MCM given the logistical challenges of medical care in a mass casualty event. Maxy-G34-treated mice that survived H-ARS were examined for residual bone marrow damage (RBMD) up to 9 mo post-exposure. Despite differences in Sca-1 expression and cell cycle position in some hematopoietic progenitor phenotypes, Maxy-G34-treated mice exhibited the same degree of hematopoietic stem cell (HSC) insufficiency as vehicle-treated H-ARS survivors in competitive transplantation assays of 150 purified Sca-1+cKit+lin-CD150+cells. These data suggest that Maxy-G34, at the dose, schedule, and time frame examined, did not mitigate RBMD but significantly increased survival from H-ARS at one-tenth the dose previously tested, providing strong support for advanced development of Maxy-G34, as well as Neulasta, as MCM against radiation. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Chua, H. L., Plett, P. A., Sampson, C. H., Katz, B. P., Carnathan, G. W., MacVittie, T. J., … Orschell, C. M. (2014). SURVIVAL EFFICACY OF THE PEGYLATED G-CSFS MAXY-G34 AND NEULASTA IN A MOUSE MODEL OF LETHAL H-ARS, AND RESIDUAL BONE MARROW DAMAGE IN TREATED SURVIVORS. Health Physics, 106(1), 10.1097/HP.0b013e3182a4df10. http://doi.org/10.1097/HP.0b013e3182a4df10 | en_US |
dc.identifier.issn | 1538-5159 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/9011 | |
dc.language.iso | en_US | en_US |
dc.publisher | Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins | en_US |
dc.relation.isversionof | 10.1097/HP.0b013e3182a4df10 | en_US |
dc.relation.journal | Health Physics | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Acute Radiation Syndrome | en_US |
dc.subject | drug therapy | en_US |
dc.subject | Bone Marrow | en_US |
dc.subject | drug effects | en_US |
dc.subject | radiation effects | en_US |
dc.subject | Granulocyte Colony-Stimulating Factor | en_US |
dc.subject | pharmacology | en_US |
dc.subject | Polyethylene Glycols | en_US |
dc.title | Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors | en_US |
dc.type | Article | en_US |