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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b
+
Gr-1
+
myeloid cells without compromising CD8
+
T cell immune responses
Journal of Hematology and Oncology, Volume 6, No. 1, Article 75, Year 2013
Notification
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Description
Background: Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo. Methods. We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice. Results: We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation. Conclusions: Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF. © 2013 Rubinstein et al.; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3850648/bin/1756-8722-6-75-S1.doc
Authors & Co-Authors
Rubinstein, Mark P.
United States, La Jolla
University of California, San Diego
United States, Charleston
Medical University of South Carolina
Salem, Mohamed Labib
United States, Charleston
Medical University of South Carolina
Egypt, Tanta
Faculty of Science
Doedens, Andrew L.
United States, La Jolla
University of California, San Diego
Moore, Caitlin J.
United States, Charleston
Medical University of South Carolina
Chiuzan, Codruta C.
United States, Charleston
Medical University of South Carolina
Rivell, Guillermo L.
United States, Charleston
Medical University of South Carolina
Cole, David J.
United States, Charleston
Medical University of South Carolina
Goldrath, Ananda W.
United States, La Jolla
University of California, San Diego
Statistics
Citations: 14
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1186/1756-8722-6-75
e-ISSN:
17568722
Research Areas
Cancer