Implementing MOA-Reflective ADCC Assays using Ready-to-Use KILR Target and Effector Cells from Screening to Lot Release
The development of antibody-based therapeutics to target the killing of tumor cells has revolutionized the space of immuno-oncology and the field of cancer therapeutics. Mechanisms by which a therapeutic antibody is able to target and kill tumor cells is critical to capture and demonstrate for Investigational New Drug (IND) applications. One of the mechanisms by which a therapeutic antibody can leverage the host immune defense and evoke target cell death is the antibody-dependent cell-mediated cytotoxicity (ADCC). Quantifying ADCC potential of an antibody therapeutic being evaluated relies on employing assays that include either radiolabeling (posing safety challenges), dye-based assays (risking the spontaneous release of dyes from the cells), or reporter gene assays (indirect MOA (mechanism-of-action)-reflective downstream detection only), all of which compromise the quality of the final data or provide non-functional output. This creates the need for a secondary bridging ADCC assay that measures direct target cell death by immune effector cells. The availability of a direct MOA-reflective ADCC assay that can be implemented from screening to characterization to potency-testing in a QC lot-release program is of paramount importance to address the market need.
This application note focuses on demonstrating the ability to measure direct target cell death mediated by ADCC via implementing an MOA-reflective cell-based assay format that offers several advantages over existing methods. This cell-based assay format (also known as the KILR® cytotoxicity assay platform) provides robustness, precision, accuracy, and demonstrates its fit-for-purpose nature from screening therapeutic antibody candidates in early drug development to characterization and potency testing in QC lot-release programs.