Optimising and validating a cell based assay for SDE-100 exemplar batch

A single ADC can have several modes of action associated with the antibody. Binding to the target may have a cytotoxic effect, perhaps by preventing dimerisation and activation of growth-factor receptors. Also, the Fc tail of the antibody may recruit cytotoxic components of the immune system via antibody dependent cellular cytotoxicity, antibody dependent phagocytosis or complement dependent cytotoxicity (CDC). In the ADC, these cytotoxic effects may be induced, in addition to the drug mediated cytotoxicity.

It may be necessary to develop a suite of cell based assays such as ADC or CDC assays in order to test the various modes of action in the ADC. In particular, where a monoclonal antibody has been shown to have a therapeutic effect it is important to establish that linking this antibody to a cytotoxin does not alter or abrogate those therapeutic modes of action.

This poster will focus on a single potency assay assessing cell death due to intracellular MMAE activity.