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Advances in the assessment and control of the effector functions of therapeutic antibodies

Nature Reviews Drug Discovery volume 10, pages 101–111 (2011)Cite this article

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Abstract

The Fc (crystallizable fragment) region of therapeutic antibodies can have an important role in their safety and efficacy. Although much is known about the structure–activity relationship of antibodies and the factors that influence Fc effector functions, a process has not yet been defined to clearly delineate how Fc functionality should be assessed and controlled during antibody development and manufacturing. In this article, we summarize the current knowledge of antibody Fc functionality, provide a strategy for assessing the effector functions of different classes of therapeutic antibodies (including Fc fusion proteins) and propose a path for routine testing and controls for manufacturers of antibody products.

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Figure 1: Classification of therapeutic antibodies based on their putative mechanisms of action.
Figure 2: Assessment and control strategies for effector functions.

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Authors and Affiliations

  1. Xu-Rong Jiang, Robert Strouse and Mark Schenerman are at Analytical Biochemistry, MedImmune, Gaithersburg, Maryland 20878, USA.,

    Xu-Rong Jiang, Robert Strouse & Mark Schenerman

  2. An Song and Shan Chung are at BioAnalytical Sciences, Genentech, South San Francisco, California 94080, USA.,

    An Song & Shan Chung

  3. Svetlana Bergelson is at Analytical Development, Biogen Idec, Cambridge, Massachusetts 02142, USA.,

    Svetlana Bergelson

  4. Thomas Arroll is at Cellular Resources, Amgen, Seattle, Washington 98119, USA.,

    Thomas Arroll

  5. Bhavin Parekh is at Bioassay Development, Eli Lilly and Company, Indianapolis 46221, USA.,

    Bhavin Parekh

  6. Kimberly May is at Biologics Manufacturing Sciences and Commercialization, Merck & Co., Union, New Jersey 07083, USA.,

    Kimberly May

  7. Anthony Mire-Sluis is at Global Product Quality and Quality Sciences, Amgen, Thousand Oaks, California 91320, USA.,

    Anthony Mire-Sluis

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Correspondence to Xu-Rong Jiang.

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Competing interests

Xu-Rong Jiang is employed by MedImmune, a wholly-owned subsidiary of AstraZeneca, and owns AstraZeneca stocks.

An Song is employed by Genentech, a member of the Roche Group and owns Roche stock.

Svetlana Bergelson is employed by Biogen Idec and owns Biogen Idec stock.

Thomas Arroll is employed by Amgen and owns Amgen stock.

Bhavin Parekh is employed by Eli Lilly and Company and owns Eli Lilly stock.

Kimberly May is employed by Merck & Co. and owns Merck stock.

Shan Chung is employed by Genentech, a member of the Roche Group, and owns Roche stock.

Robert Strouse is an employee of MedImmune, a wholly-owned subsidiary of AstraZeneca. He owns stocks in AstraZeneca.

Anthony Mire-Sluis is employed by Amgen and owns Amgen stock.

Mark Schenerman is employed by MedImmune, a wholly-owned subsidiary of AstraZeneca, and owns AstraZeneca stocks.

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Jiang, XR., Song, A., Bergelson, S. et al. Advances in the assessment and control of the effector functions of therapeutic antibodies. Nat Rev Drug Discov 10, 101–111 (2011). https://doi.org/10.1038/nrd3365

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