title: Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte-macrophage colony-stimulating factor.
abstract: Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) can be expressed in yeast, bacteria, or mammalian cells. Expression in each system results in a protein that differs, to a varying extent, from native GM-CSF. Like the native protein, yeast-expressed GM-CSF is glycosylated and has 127 amino acids, but differs from native GM-CSF in molecular mass and in the substitution of leucine for proline at position 23. GM-CSF expressed in Escherichia coli bacteria is not glycosylated, has six fewer amino acids than the native protein, and an extra methionine at position 1. A review of laboratory studies shows that these differences in physiochemical properties result in variations in the pharmacokinetics, biologic activity, and immunogenicity of GM-CSF expressed in different host cells. These variations may lead to an increased clinical toxicity with GM-CSF expressed in E coli versus that produced in yeast. A total of 32 clinical trials were reviewed to determine the relative frequency of adverse events in patients treated with GM-CSF expressed in E coli versus that expressed in yeast. In general, the median reported frequency of adverse events was higher in patients treated with E coli-derived GM-CSF. The median frequencies of fluid retention, dyspnea, fever, myalgias/bone pain/joint pain, and rash were 8.3%, 13.4%, 21.7%, 16%, and 14.3%, respectively, in patients receiving GM-CSF expressed in yeast, versus 18.4%, 55.2%, 40.7%, 28.5%, and 12.5%, respectively, in patients treated with GM-CSF expressed in E coli. Thus data in the literature support the view that the GM-CSF expression system influences the pharmacokinetic properties, biologic activity, and clinical toxicity of GM-CSF.
authors.affiliation: Arizona Cancer Center, Tucson.
authors.forename: R T
authors.initials: RT
authors.lastname: Dorr
mesh_terms: D004926:Escherichia coli; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000633:toxicity; D015003:Yeasts
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor