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

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 fro
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 orroborated in humans.
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Author:Darja Karpova, Katrin Dauber, Gabriele Spohn, Doreen Chudziak, Eliza Wiercinska, Miriam Schulz, Allison R. Pettit, Jean-Pierre Levesque, Barbara Romagnoli, Kalpana Patel, Eric Chevalier, Klaus Dembowsky, Halvard-Björn Bönig
URN:urn:nbn:de:hebis:30:3-317183
DOI:http://dx.doi.org/10.1038/leu.2013.266
ISSN:1476-5551
ISSN:0887-6294
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24072044
Parent Title (English):Leukemia
Publisher:Nature Publ. Group
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2013/09/27
Date of first Publication:2013/09/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/10/07
Tag:CXCL12; CXCR4; G-CSF; hematopoietic stem and progenitor cells; mobilization
Volume:27
Issue:12
Pagenumber:10
First Page:2322
Last Page:2331
Note:
This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
HeBIS PPN:353305308
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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