DM: Yes, there are in fact suites of functional assays for mAbs of different isotypes. For example, IgG1 mAbs, the most common, are typically evaluated for their ability to induce antibody dependent cellular cytotoxicity (ADCC), as well as complement dependent cytotoxicity (CDC). Moreover, the ability of this class of mAbs to bind Fc receptors is also routinely measured.
Unique to each mAbs and or non-mAb is its mechanism of action, which is often characterized by its ability to induce a cytotoxic or anti proliferative effect on a target cell. But this is a broad generalization since many mAbs and non-mAbs are now designed to bind certain cellular receptors and turn on or off signals that modulate the immune response. Therefore, these biotherapeutics are not necessarily killing a target cell but rather tricking it into acting a certain way. In all cases, sophisticated and sometimes very complex cell-based assays need to be developed to measure the bioactivity of a mAb or non-mAb.
These assays are often complemented with assays that measure the relative levels of cytokines and other immune modulators. In many instances now, we are seeing bioassays that consists of two parts: Part a) treat the cells with the mAb or non-mAb and Part b) measure the immune-response.
FG: Thanks for this explanation, Dan. I understand that BioPharmaSpec and Custom Biologics have developed a useful Quick Guide for companies developing biosimilars to answer this very question about typical assay requirements for functional and structural characterization. Thanks again for taking the time to participate in this most recent Biosimilars Roundtable!