Recombinant human GM-CSF

Autologous bone marrow transplantation involves initial removal of some marrow from the patient, its storage in liquid nitrogen, followed by its re-introduction into the patient subsequent to chemo- or radiotherapy. Leukine is the tradename given to a recombinant human GM-CSF preparation produced in engineered S. cerevisiae (Table 6.4). 

Robison RL, Myers LA. Preclinical safety assessment of recombinant human GM-CSF in rhesus monkeys. Int Rev Exp Pathol 1993 34A 149,172. 

Gribben JG, Devereux S, Thomas NS, Keim M, Jones HM, Goldstone AH, Linch DC. Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF. Lancet 1990 335(8687) 434-7. 

Macrophage colony-stimulating factor (M-CSF) stimulates the growth and differentiation of the monocyte lineage, and promotes the survival, proliferation, and functions of mature monocytes/macrophages (1). It also enhances myelopoiesis through the amplified production of G-CSF and GM-CSF by monocytes, and has antitumor activity. Purified human urinary M-CSF and recombinant human M-CSF are under investigation in humans. 

Kreitman, R. J. and Pastan, I. (1997) Recombinant toxins containing human GM-CSF and either Pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukemia cells. Blood 90,252-259. 

Recombinant GM-CSF (produced in Escherichia coli, yeast or COS cells) has been tested for its ability to affect haematopoiesis in primates and humans. Because of its relatively short half-life in the circulation, daily administration (usually via intravenous infusion) is required. Administration results in a transient neutropenia, monocytopenia and eosinopenia within 30 min of administration, presumably because of the ability of GM-CSF to stimulate the expression of adhesins and hence increase the numbers of leukocytes adhered to the capillary endothelium in the marginated pool. Additionally, these leukocytes may accumulate in the lungs after GM-CSF administration, which may contribute to the decrease in the observed numbers... 

Vadas, M. A. (1988). Recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) regulates fMet-Leu-Phe receptors on human neutrophils. Immunol. 64,519-25. 

NK cells express receptors for numerous monokines constitutively, and produce IFN-y and other NK-derived cytokines rapidly in response to stimulation by monokines [18, 19]. Freshly isolated CD56 "s human NK cells are the primary source of NK cell-derived immuno-regulatory cytokines, including IFN-y, TNF-(3 (lymphotoxin), IL-10, IL-13 and GM-CSF, whereas the CDSb NK-cell subset produces consistently negligible amounts of these cytokines following stimulation with recombinant monokines in vitro [20]. The production of cytokines by NK cell subsets was investigated following activation with phorbol esters (e.g. phorbol 12-myristate 13-acetate (PMA)) and ionomycin. 

A. General description Sargramostim (GM-CSF) is a recombinant human granulocyte-macrophage colony-... 

Hematologic and coagulation factors Sargramostatin, human recombinant GM-CSF, produced in a yeast (5. cerevisiae) expression system Leukine 19.5,16.8,15.5 (mixture) Mobilization of hematopoietic progenitor cells into peripheral blood... 

A. Tsarbopoulos, B. N. Pramanik, J. Labdon, P. Reichert, G. Gitlin, S. Patel, V. Sardana, T. L. Nagabhushan, and P. P. Trotta, Isolation and characterization of a resistant core peptide of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) confirmation of the GM-CSF amino acid sequence by mass spectrometry. Protein Sci. 2 (1993), 1948-1958. 

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