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Bioengineering 2017, 4(2), 42; doi:10.3390/bioengineering4020042

Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

Glycotope GmbH, Robert-Roessle-Street 10, 13125 Berlin, Germany
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Academic Editors: Stephan Hinderlich and Hans Henning von Horsten
Received: 14 March 2017 / Revised: 30 April 2017 / Accepted: 2 May 2017 / Published: 8 May 2017
(This article belongs to the Special Issue Recombinant Glycoproteins)
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Abstract

IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich) and hematological (CD20) cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated. View Full-Text
Keywords: IgA antibody; cancer therapy; human expression system; human glycosylation; glyco-optimization; perfusion process; TA-mucin 1; Her2; EGFR; Thomsen–Friedenreich; CD20 IgA antibody; cancer therapy; human expression system; human glycosylation; glyco-optimization; perfusion process; TA-mucin 1; Her2; EGFR; Thomsen–Friedenreich; CD20
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hart, F.; Danielczyk, A.; Goletz, S. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy. Bioengineering 2017, 4, 42.

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