Macrophage/neutrophil functional assays

In vitro or ex vivo macrophage/neutrophil functional assays including ADCC, phagocytosis, oxidative burst, and chemotaxis. 

During the safety evaluation of therapeutics, toxicities that are specific to innate immunity may be observed and there are specific assays available to determine which aspect of innate immunity is affected. These assays include NK cell, macrophage and neutrophil function assays, and the assessment of soluble mediators in serum. A selection of these assays will be described in this section. 

In order to understand potential immunotoxicity observed during the safety evaluation of therapeutics, assays are available to assess whether specific components of innate immunity are affected. These assays include functional assays for the cell types involved in this phase of the immune response (NK cells, macrophages, and neutrophils) and measurement of complement proteins. The majority of these assays may be incorporated into toxicity studies thereby allowing for simultaneous measurement of specific immunotoxicologi-cal end points within the same study as toxicological end points. 

Some examples of in vitro assays for immunotoxicity assessment follow (Table 13.1), but this list is not intended to be comprehensive. It should be borne in mind that this is a rapidly growing area of research, and many of the assays employed in immunotoxicity or immunosafety evaluation of pharmaceuticals are fit-for-purpose assays based on mechanism or target and are beyond the scope of this chapter. Evaluation of effects on individual cell types and mechanisms (e.g., neutrophil, macrophage, cytotoxic T lymphocyte, and NK function) will not be discussed, as these are rarely employed unless driven by STS findings or intended mechanism of action. 

---