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Anti-galactose-α-1,3-galactose IgE from allergic patients does not bind α-galactosylated glycans on intact therapeutic antibody Fc domains

Nature Biotechnology volume 29, pages 574–576 (2011)Cite this article

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To the Editor:

Manufacture of monoclonal antibodies (mAb) and related biologics is performed in eukaryotic cell lines to allow proper glycosylation, which is often critical for function. The first mAbs were produced in the mouse-derived cell lines SP2/0 and NS0, which have the genetic makeup to produce proteins containing nonhuman glycan structures, such as galactose-α-1,3-galactose (α-Gal) and N-glycolylneuramic acid1, that can adversely affect safety and half-life. The best example is Erbitux (cetuximab), produced in SP2/0 cells, clinical use of which has been associated with α-Gal–specific, IgE-mediated anaphylactic responses2. In addition, patients with IgE antibodies to α-Gal may experience allergic reactions to red meat3,4. The quantity of α-Gal required to induce hypersensitivity reactions is not known; however, it is clear that binding of IgE antibodies against α-Gal is an important trigger in this pathology2.

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Figure 1: Binding of IgE antibodies in serum samples of 20 meat allergy patients to therapeutic mAbs in different production systems and the interaction of cetuximab, infliximab or isolated fragments thereof with α-Gal–specific IgE measured in an IgE inhibition RIA.

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Acknowledgements

We thank M. Geukes, A.H. Simmelink and N.I.L. Derksen for valuable technical assistance, and R. Taylor for his enthusiastic support.

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Author notes

  1. Jeroen J Lammerts van Bueren and Theo Rispens: These authors contributed equally to this work.

Authors and Affiliations

  1. Genmab, Utrecht, The Netherlands

    Jeroen J Lammerts van Bueren, Sandra Verploegen, Patrick H C van Berkel, Jan G J van de Winkel & Paul W H I Parren

  2. Sanquin Research, Amsterdam, The Netherlands

    Theo Rispens, Tjitske van der Palen-Merkus & Steven Stapel

  3. Asthma and Allergic Diseases Center, University of Virginia, Charlottesville, Virginia, USA

    Lisa J Workman, Hayley James & Thomas A E Platts-Mills

  4. Department of Immunology, Immunotherapy Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands

    Jan G J van de Winkel

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Correspondence to Paul W H I Parren.

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J.J.L.v.B., S.V., P.H.C.v.B, J.G.J.v.d.W. and P.W.H.I.P. are Genmab employees and Genmab warrants and/or stock. T.R. has received research support rhgouh his institution from Genmab.

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van Bueren, J., Rispens, T., Verploegen, S. et al. Anti-galactose-α-1,3-galactose IgE from allergic patients does not bind α-galactosylated glycans on intact therapeutic antibody Fc domains. Nat Biotechnol 29, 574–576 (2011). https://doi.org/10.1038/nbt.1912

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