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HemaCare Immune Cells Ace Cytotoxicity Assay used to Screen Therapeutic Antibodies

Jan 22, 2019, 10:15:00 AM / by Nancy Andon, MSc

blog-immune-cells-1In an independent study recently published by Pfizer, [1] natural killer (NK) immune cells sourced from HemaCare were evaluated to test how well suited they are for use in cytotoxic activity assays.

These last few years have seen the successful clinical development of several monoclonal antibody-based treatments for cancer and inflammatory disease. These antibodies are designed to act in a number of different ways, from tagging target cells so they can be recognized by the immune system, to blocking growth or metastasis, to attacking problematic cells themselves. Monoclonal antibodies (m’Abs) are seen as particularly beneficial because they can be used to complement more traditional therapies and because their use generally results in fewer side effects.

One of the most important methods of action (MOA) of therapeutic m’Abs involves binding to an “effector cell”, which is an immune system cell that directly attacks cancer cells or other dysfunctional cells in the body. Briefly, the binding of the antibody to both the target cell and an immune effector cell activates the immune cell.  This activation results in the release of cytotoxic enzymes and other immune modulators that mediate the destruction of the target cell (for example a cancer cell). This particular MOA is called antibody-dependent cell-mediated cytotoxicity (ADCC) and is induced by natural killer cells and other effector cell types.

Not all effector cells are the same, however. Modifications on the antibody receptors of effector cells affect the cell’s biological activity and can influence clinical outcomes. [2] This means that some effector cells may be more suitable than others for measuring ADCC activity during therapeutic antibody development. The research group at Pfizer set out to do a side-by-side comparison of two different versions of a common antibody receptor expressed in three types of effector cells commonly used in ADCC activity assays. Their goal was to assess similarities and differences between effector cell types and relate this information to application of ADCC assays during drug development.

To carry out their biological activity assays, the authors chose primary NK cells from two different donors through HemaCare. These donor cells expressed two different versions of a common antibody receptor. In parallel to this experiment, the authors assessed engineered NK cell and engineered Jurkat T cell lines. Both cell lines were engineered to express the same two versions of the antibody receptor found in the primary cells, for a total of 6 preparations in all.

After carrying out a number of biological activity assays, the scientists found that primary NK cells and one version of the engineered NK cells had the highest cell surface receptor expression, binding, and cytotoxic potency, while engineered Jurkat cells with either version of the antibody receptor had lower surface expression, and only a fraction of the cytotoxic potency of the NK cells. They determined that using primary NK cells or engineered NK cells with the more effective version of receptor type would give more physiologically relevant results in an ADCC assay, though Jurkat cells are certainly still useful for other applications. More effective evaluation assays in turn leads to better assessment of therapeutic potency.

Physiological relevance, cell purity, and reproducibility all make a big difference in cell therapy process development and commercialization. To learn more about HemaCare’s wide selection of cell related products and services, please visit our website.

Reference:

  1. Hsieh Y, et al. Characterization of FcγRIIIA effector cells used in in vitro ADCC bioassay: Comparison of primary NK cells with engineered NK-92 and Jurkat T cells. Journal of Immunological Methods. 441; 56-66. Feb. 2017.
  2. Rodríguez J, et al. Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer. Eur. J. Cancer 48 (12), 1774. 2012.

Topics: Assay Development, NK Cells

Nancy Andon, MSc

Written by Nancy Andon, MSc

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