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[PEGS 2021] Quantify Diverse Immune Cell-Mediated Killing Mechanisms: Applications of a Robust, Non-Radioactive KILR Cytotoxicity Platform

[PEGS 2021] Quantify Diverse Immune Cell-Mediated Killing Mechanisms: Applications of a Robust, Non-Radioactive KILR Cytotoxicity Platform
Year:
2021

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The clinical success of an ever-increasing array of biologics has led to the development of a wide spectrum of immunomodulatory agents with distinct mechanisms of action (MOA) targeting novel antigens. These biologics 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. During the development of such therapeutics, classical antibody (Fc) effector functions are monitored, such as antibody dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the measurement of another type of effector-mediated killing, known as antibody-dependent cellular phagocytosis (ADCP) has gained traction. Here, we present KILR®, a novel cytotoxicity assay platform technology that specifically measures killing of target cancer cells in a co-culture with immune cells, in an easy-to-use, dye-free, and radioactivity-free assay. Based on the industry-validated Enzyme Fragment Complementation (EFC) technology, the KILR platform is useful for 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. Generating a very low background, these assays produce robust assay windows with excellent precision, and are applicable to various stages of drug development, ranging from screening to use in QC lot release of complex biologic drugs. KILR Cytotoxicity Assays have been tested using multiple primary effector cells (PBMCs, Macrophages, and NKs) and engineered cells lines (NK-92). Further, these assays can be used to evaluate other immunotherapy drugs such as T-cell redirecting bi-specific antibodies and chimeric antigen receptor T-cells (CAR-T), and tumor-infiltrating lymphocytes (TILs).