[BEBPA 2017] Driving Robust and Reproducible ADCC and T Cell Redirection with Single Donor KILR® CD16 Effector Cells
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- BEBPA 2017
Class I therapeutic antibodies achieve their clinical efficacy not only by binding to their target antigen, but also through Fc domain-mediated recruitment of immune cell effectors to attack and kill the target cell. Therefore, developers of therapeutic antibodies must assess all possible mechanisms of action (MOA) of their molecules, including antibody-dependent cell-mediated cytotoxicity (ADCC). Success of ADCC assays is highly dependent on the quality of effectors used. However, primary human cells (such as PBMCs or NK cells) suffer from inter-individual or donor variability, while NK cell lines often show high background lysis in susceptible cell models and functional variability under different culture conditions.
In this poster, we present data on cytotoxicity assays using single donor-derived, engineered effector cells, the KILR CD16 T Effector Cells that stably express CD16. These uniformly manufactured cells maintain their T cell phenotype (TCRab -, CD3- and CD8-positive) after transfection. Importantly, CD16 expression and killing capacity are consistent across multiple batches of manufactured cells. When used in ADCC assays, these effector cells produce very low background, resulting in robust assay windows, with excellent repeatability and precision, making these cells well-suited for characterization and lot release assays. Further, we demonstrate that these effector cells are compatible with T cell redirection applications, using the clinical molecule blinatumomab.