title: 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.
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.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Rubinstein
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Salem
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Doedens
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Moore
authors.forename: Cody
authors.initials: C
authors.lastname: Chiuzan
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Rivell
authors.forename: David J
authors.initials: DJ
authors.lastname: Cole
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D016179:Granulocyte Colony-Stimulating Factor