A novel CXCR4 antagonist for hematopoietic stem cell mobilization
1Genzyme Corp., Framingham, MA 01701-9322, USA. simon.fricker@genzyme.com
Background:
Hematopoietic stem cell (HSC) transplantation is a treatment option for hematological malignancies. Current mobilization regimes frequently result in inadequate numbers of HSC for transplant therefore alternative methods of mobilization are required.
Objective:
The chemokine receptor CXCR4 and ligand SDF-1 are integrally involved in HSC homing and mobilization. Disruption of the SDF-1/CXCR4 axis by the CXCR4 anatagonist, plerixafor, is shown to improve HSC mobilization.
Methods:
The molecular and in vivo pharmacology of plerixafor and subsequent clinical development is reviewed.
Results/Conclusion:
Preclinical studies demonstrate that plerixafor is a selective antagonist of CXCR4 and can rapidly mobilize HSC. Clinical trials demonstrated improved HSC mobilization when plerixafor was included in the mobilization regimen. These data suggest the potential for a significant role for plerixafor in hematological disease.
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