Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF.
In 4 out of 16 patients receiving recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) in phase I/II studies antibodies developed to the recombinant protein. The antibodies react with sites on the native protein backbone which are normally protected by O-linked glycosylation but which are exposed in rhGM-CSF produced in yeast and Escherichia coli. Antigenicity of recombinant human proteins due to non glycosylation may have relevance to the choice of host system for production of factors for clinical use.
Gribben
J G
JG
Department of Haematology, Faculty of Clinical Sciences, University College and Middlesex School of Medicine, London, UK.
Devereux
S
S
Thomas
N S
NS
Keim
M
M
Jones
H M
HM
Goldstone
A H
AH
Linch
D C
DC
D000906:Antibodies / Q000032:analysis*; D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D001666:Binding Sites, Antibody / Q000276:immunology*; D015153:Blotting, Western / Q000379:methods; D001856:Bone Marrow Examination / Q000379:methods; D002986:Clinical Trials as Topic; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004926:Escherichia coli; D006031:Glycosylation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007262:Infusions, Intravenous; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D013997:Time Factors; D015003:Yeasts
D000906:Antibodies; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor