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[Biologics Biosimilars Congress 2017] Specifically Measure Target Cell Death in a Co-Culture with ImmuneCells Through a Non-Radioactive, Dye-Free Cytotoxicity Assay

[Biologics Biosimilars Congress 2017] Specifically Measure Target Cell Death in a Co-Culture with ImmuneCells Through a Non-Radioactive, Dye-Free Cytotoxicity Assay
Version:
20721

File Name/Number:
2017 Biologics & Biosimilars Congress

Year:
2017

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Following the recent regulatory approvals of a number of checkpoint inhibitor therapeutics,
development of a wide array of immunomodulatory therapeutic antibodies targeting novel antigens and with distinct mechanisms of action (MOA) have emerged. These include classical
monoclonal antibodies, but also increasingly bi- and multi-specific antibodies designed
to redirect T-cells to tumors and modulate anti-tumor T-cell responses. In addition to the classical antibody (Fc) effector functions that developers must monitor, such as Antibody dependent cell-mediated cytotoxicity (ADCC) and Complement-dependent cytotoxicity
(CDC), there is increasing interest in following another type of effector mediated killing, known
as Antibody-dependent cellular phagocytosis (ADCP). Here, we present a novel cytotoxicity
assay using our proprietary enzyme fragment complementation (EFC) technology that specifically measures killing of target cancer cells in a co-culture with immune cells, in an easy
to use, dye-free & radioactivity-free assay. Importantly, the same technology is applicable to
multiple applications such as ADCC, CDC, ADCP and T-cell redirection. We discuss examples
where the same engineered target cell line is used to determine ADCC, CDC and ADCP
capabilities of an antibody drug. These assays have very low background, thus producing
robust assay windows, with excellent precision, and are applicable to multiple stages of
drug development, ranging from screening to use in QC lot release of these complex biologic
drugs. This assay has been tested using multiple primary effector cells (PBMCs, Macrophages
and NKs) or engineered cells lines (NK92). Further, this assay is applicable to other
immunotherapy drugs such as T-cell redirecting bi-specific antibodies and chimeric antigen
receptor T-cells (CAR-T).