The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Karpova, D., Dauber, K., Spohn, G., Chudziak, D., Wiercinska, E., Schulz, M., Pettit, A. R., Levesque, J. P., Romagnoli, B., Patel, K., Chevalier, E., Dembowsky, K. and Bonig, H. (2013) The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor. Leukemia, 27 12: 2322-2331. doi:10.1038/leu.2013.266


Author Karpova, D.
Dauber, K.
Spohn, G.
Chudziak, D.
Wiercinska, E.
Schulz, M.
Pettit, A. R.
Levesque, J. P.
Romagnoli, B.
Patel, K.
Chevalier, E.
Dembowsky, K.
Bonig, H.
Title The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor
Journal name Leukemia   Check publisher's open access policy
ISSN 0887-6924
1476-5551
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/leu.2013.266
Volume 27
Issue 12
Start page 2322
End page 2331
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2014
Language eng
Formatted abstract
Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and
allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be corroborated in humans.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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Created: Tue, 03 Dec 2013, 00:03:00 EST by Roheen Gill on behalf of UQ Centre for Clinical Research