Influence of variable N-glycosylation on the cytolytic potential of chimeric CD19 antibodies

Journal of Immunotherapy
Karin BarbinG H Fey

Abstract

To investigate the influence of N-linked oligosaccharides at asparagines-297 on the cytolytic potential of chimeric CD19 antibodies, three distinct variants were generated by production in different expression systems. The same chimeric CD19 antibody was produced in Sf21 insect cells, human 293 T cells, and 293 T cells expressing a co-transfected beta1,4-N-acetylglucosaminyltransferase III (GnTIII). The N-glycan structures and the cytolytic potential of the antibodies produced in these three systems were directly compared. After expression in insect cells, the antibody carried paucimannosidic N-linked oligosaccharides, distinct from the complex biantennary carbohydrate moieties attached to the product from human cells. After co-expression with GnTIII in human cells, the antibody carried an eightfold greater percentage of oligosaccharides with a bisecting N-acetylglucosamine (78.7% versus 9.6%) and a 30-fold increased proportion of bisecting, defucosylated oligosaccharides (15.9% versus 0.5%). The insect cell product triggered stronger antibody-dependent cellular cytotoxicity (ADCC) of a human leukemia-derived cell line than the product from non-re-engineered 293 T cells and was equally effective at 50- to 100-fold lower concent...Continue Reading

References

Aug 1, 1992·European Journal of Biochemistry·E StaudacherL März
Jan 1, 1991·Cancer Immunology, Immunotherapy : CII·A HekmanC J Melief
Dec 1, 1991·Immunology and Cell Biology·H ZolaY Kurosawa
Jan 1, 1993·Springer Seminars in Immunopathology·A Wright, S L Morrison
Jul 1, 1995·Cancer Immunology, Immunotherapy : CII·G A PieterszJ A Trapani
Aug 1, 1995·Leukemia & Lymphoma·R H Scheuermann, E Racila
Jan 1, 1997·Trends in Biotechnology·A Wright, S L Morrison
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A GhetieE S Vitetta
Oct 6, 1999·Current Opinion in Immunology·M S CraggM J Glennie
Dec 28, 1999·Glycoconjugate Journal·F AltmannL März
Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Apr 12, 2001·The Journal of Biological Chemistry·S RadaevP D Sun
Mar 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Klaus TirochThomas Valerius
Apr 18, 2002·Bone Marrow Transplantation·P LangD Niethammer
Nov 26, 2002·Hematology·Dieter HoelzerTomasz Szczepański
Sep 17, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wen-Kai Weng, Ronald Levy

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Citations

Aug 1, 2007·Cancer Immunology, Immunotherapy : CII·Julia StieglmaierWijnand Helfrich
May 7, 2013·Current Opinion in Structural Biology·Steven C AlmoStephen K Burley
May 29, 2012·Archives of Biochemistry and Biophysics·Andreas Loos, Herta Steinkellner
Oct 27, 2017·Transfusion Medicine and Hemotherapy : Offizielles Organ Der Deutschen Gesellschaft Fur̈ Transfusionsmedizin Und Immunham̈atologie·Christian KellnerMatthias Peipp
Oct 28, 2010·Journal of Environmental Monitoring : JEM·Linda G T GainesLeena A Nylander-French
Dec 13, 2007·The Journal of Clinical Endocrinology and Metabolism·Sandra A RebuffatSylvie Peraldi-Roux
Jul 26, 2019·Cancers·Ziqing ChenAndreas Lundqvist
Aug 2, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Elsa Wagner-RoussetAlain Beck

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