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Research Article

Overcoming soluble target interference in an anti-therapeutic antibody screening assay for an antibody–drug conjugate therapeutic

    Montserrat Carrasco-Triguero

    * Author for correspondence

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

    ,
    Connie Mahood

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    ,
    Marija Milojic-Blair

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    ,
    Caroline Amaya

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    ,
    Jane Ruppel

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    ,
    Kyu Hong

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    ,
    Joo-Hee Yi

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    &
    Surinder Kaur

    Bioanalytical Sciences Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    Published Online:https://doi.org/10.4155/bio.12.165

    Background: The standard safety evaluation of biotherapeutics includes assessment of immunogenicity. Anti-therapeutic antibodies (ATA) can be detected in serum using immunoassays with a bridging format. However, these assays can be subject to interference. Results: In the bridging ATA assay for 3A5 TDC, an antibody–drug conjugate that binds to the multimeric extracellular domain of MUC16 (CA125), soluble CA125 in the serum caused false-positive results by binding to the ATA assay reagents. This interaction was blocked by wheat germ agglutinin lectin as it binds to the glycans in CA125; thus, the specificity of the assay improved. Conclusion: The assay development and validation results showed that the addition of wheat germ agglutinin eliminates the interference from circulating CA125 without impacting the ability to detect ATA.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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