Reasearch Awards nomination

Email updates

Keep up to date with the latest news and content from Journal of Hematology & Oncology and BioMed Central.

Open Access 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

Mark P Rubinstein123*, Mohamed L Salem24, Andrew L Doedens1, Caitlin J Moore2, Cody Chiuzan5, Guillermo L Rivell2, David J Cole2 and Ananda W Goldrath1

Author Affiliations

1 Department of Biological Sciences, The University of California, San Diego, La Jolla, CA 92093, USA

2 Department of Surgery, Medical University of South Carolina, Charleston, SC 29403, USA

3 Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, 86 Jonathan Lucas Street, HO506, SC 29403, USA

4 Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt

5 Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA

For all author emails, please log on.

Journal of Hematology & Oncology 2013, 6:75  doi:10.1186/1756-8722-6-75

Published: 1 October 2013

Abstract

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.

Keywords:
G-CSF; Myeloid cells; Antibody/cytokine complexes; Pegylation; Neutrophils; Neupogen; Neulasta; Protein therapeutics