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DuoMab: a novel CrossMab-based IgG-derived antibody format for enhanced antibody-dependent cell-mediated cytotoxicity

Sustmann, Claudio and Dickopf, Steffen and Regula, Jörg T. and Kettenberger, Hubert and Mølhøj, Michael and Gassner, Christian and Weininger, Diana and Fenn, Sebastian and Manigold, Tobias and Kling, Lothar and Künkele, Klaus-Peter and Schwaiger, Manfred and Bossenmaier, Birgit and Griese, Julia J. and Hopfner, Karl-Peter and Graff-Meyer, Alexandra and Stahlberg, Henning and Ringler, Philippe and Lauer, Matthias E. and Brinkmann, Ulrich and Schaefer, Wolfgang and Klein, Christian. (2019) DuoMab: a novel CrossMab-based IgG-derived antibody format for enhanced antibody-dependent cell-mediated cytotoxicity. mAbs, 11 (8). pp. 1402-1414.

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Official URL: https://edoc.unibas.ch/72052/

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Abstract

High specificity accompanied with the ability to recruit immune cells has made recombinant therapeutic antibodies an integral part of drug development. Here we present a generic approach to generate two novel IgG-derived antibody formats that are based on a modification of the CrossMab technology. MoAbs harbor two heavy chains (HCs) resulting in one binding entity and one fragment crystallizable region (Fc), whereas DuoMabs are composed of four HCs harboring two binding entities and two Fc regions linked at a disulfide-bridged hinge. The latter bivalent format is characterized by avidity-enhanced target cell binding while simultaneously increasing the 'Fc-load' on the surface. DuoMabs were shown to be producible in high yield and purity and bind to surface cells with affinities comparable to IgGs. The increased Fc load directed at the surface of target cells by DuoMabs modulates their antibody-dependent cell-mediated cytotoxicity competency toward target cells, making them attractive for applications that require or are modulated by FcR interactions.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Taylor & Francis
ISSN:1942-0862
e-ISSN:1942-0870
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:18 Aug 2020 12:47
Deposited On:18 Aug 2020 12:47

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