Functional assays

Functional assays

Recent success of molecules targeting immune checkpoints involved in T cell responses, such as Yervoy (Ipilimumab, anti-CTLA4), Keytruda (Pembrolizumab, anti-PD1), Opdivo (Nivolumab, anti-PD1) or Bavenico (Avelumab, anti-PD-L1) in cancer patients have revived the field of immunotherapeutic approaches in oncology and more particularly of Immune Checkpoint Inhibitors (ICI).

At different levels of the immune system, as soon as an activation signal is delivered, inhibitory mechanisms get engaged to contain adverse effects of an exacerbated immune response (e.g. inflammatory diseases, autoimmunity….).

T cells and NK cells display potent immune defenses by releasing lysosomal granule contents such as granzymes and perforin. Lysosomes containing these cytotoxic granules move to the cell surface and fuse with the plasma membrane to release their contents upon specific receptor engagement between a target cell and cytotoxic cell. ABL has developed and validated flow cytometry assays to measure this transient cytotoxic cell degranulation.

For example, by measuring the CD107a degranulation and the capacity of NK cells to produce IFN-gamma in response to target cells, one can evaluate the cytotoxic function of NK cells, either direct or by Antibody-Directed Cell Cytotoxicity (ADCC). In the following case study, the candidate antibody targets an inhibitory receptor on NK cells and enhances their cytotoxic function, as demonstrated by increased frequency of CD107a/b positive cells and of IFN-g secreting cells. ABL developed this assay in the context of a longitudinal clinical study. This representative example illustrates the low variability of the assay when performed by 2 different operators in 5 independent series of experiments on one reference sample.

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