[SLAS 2017] Specifically Measure Target Cell Death in a Co-Culture with Immune Cells Through a Non-Radioactive, Dye-Free Cytotoxicity Assay
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
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- 2017 SLAS Conference Poster
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).