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Promegapoietin‐1a, an Engineered Chimeric IL‐3 and Mpl‐L Receptor Agonist, Stimulates Hematopoietic Recovery in Conventional and Abbreviated Schedules Following Radiation‐Induced Myelosuppression in Nonhuman Primates
- Source :
- STEM CELLS. 19:329-338
- Publication Year :
- 2001
- Publisher :
- Oxford University Press (OUP), 2001.
-
Abstract
- Promegapoietin-1a (PMP-1a), a multifunctional agonist for the human interleukin 3 and Mpl receptors, was evaluated for its ability to stimulate hematopoietic reconstitution in nonhuman primates following severe radiation-induced myelosuppression. Animals were total body x-irradiated (250 kVp) to 600 cGy total midline tissue dose. PMP-1a was administered s.c. in several protocols: A) daily (50 microg/kg) for 18 days; B) nine doses (5 microg/kg) every other day for 3 weeks; C) a single high dose (100 microg/kg) at 20 hours, or D) a single high dose (100 microg/kg) at 1 hour following TBI. The irradiation controls received 0.1% autologous serum for 18 consecutive days. Hematopoietic recovery was assessed by bone marrow clonogenic activity, peripheral blood cell nadirs, duration of cytopenias, time to recovery to cellular thresholds, and requirements for clinical support. PMP-1a, irrespective of administration schedule, significantly improved all platelet-related parameters: thrombocytopenia was eliminated, the severity of platelet nadirs was significantly improved, and recovery of platelet counts toor =20,000/miccrol was significantly reduced in all PMP-1a-treated cohorts. As a consequence, all PMP-1a-treated cohorts were transfusion-independent. Neutrophil regeneration was augmented in all treatment schedules. Additionally, all PMP-1a-treated cohorts showed an improvement in red blood cell nadir and recovery. PMP-1a in conventional or abbreviated schedules induced significant thrombopoietic regeneration relative to the control cohort, whereas significant improvement in neutrophil recovery was schedule-dependent in radiation-myelosuppressed nonhuman primates.
- Subjects :
- Male
Agonist
Erythrocytes
Neutropenia
medicine.drug_class
Recombinant Fusion Proteins
Biology
Promegapoietin
Pharmacology
Protein Engineering
Drug Administration Schedule
medicine
Animals
Humans
Platelet
Peripheral blood cell
Clonogenic assay
Receptor
Interleukin 3
Cell Biology
Hematopoietic Stem Cells
Macaca mulatta
Thrombocytopenia
Peptide Fragments
Receptors, Interleukin-3
Hematopoiesis
Drug Combinations
medicine.anatomical_structure
Thrombopoietin
Immunology
Molecular Medicine
Interleukin-3
Bone marrow
Peptides
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 15494918 and 10665099
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- STEM CELLS
- Accession number :
- edsair.doi.dedup.....b768cc1a8fc1d859334857dedd9ab291