Measurement of Fc-mediated antibody-mediated cellular cytotoxicity (ADCC) during antibody drug discovery and development is important for antibodies that use ADCC as their primary mechanism of action as well as for antibodies designed to target and block soluble ligands.
The iLite ADCC Reporter Bioassay is designed for evaluating ADCC of therapeutic monoclonal antibodies (mAbs) and exhibits greatly reduced variability and offers an easier workflow than traditional ADCC assays.
Many therapeutic monoclonal antibodies (mAbs) include ADCC as part of their mechanism of action (MoA). This makes accurate determination of ADCC activity an essential part of the development and characterization of therapeutic antibodies.
When investigating potential drug candidates, it is essential to determine the presence of ADCC activity and if found, quantify the activity. This is an important step in identifying the most potent antibody and in lot release testing. If ADCC has been determined to be the mechanism of action of a biological drug this should be reflected in the potency assay.
To increase the ADCC activity of therapeutic antibodies, the pharmaceutical industry has structurally improved the Fc region of the antibodies. Point mutations or modifications into the glycosylation profiles of Fc regions have been shown to increase their affinity towards Fc receptors on a range of effector cells. To evaluate the efficacy of these biotherapeutics, several ADCC methodologies have been developed.
Using iLite® assays, we have shown that deglycosylation of the therapeutic antibodies trastuzumab and rituximab using GlycINATOR enzyme (Genovis) completely abolishes ADCC. This workflow represents a powerful tool in preclinical development and mode-of-action studies of therapeutic antibody candidates.
With many of the existing patents of monoclonal antibody block buster drugs set to expire in the next few years, the development of biologic therapeutics similar to the original drug (biosimilars) has become increasingly important.
However, extensive requirements for analytical characterization is needed to show comparability between innovator and biosimilar and it must be proven that “the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components” and that “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency”. This is the biosimilar development approach from the EMA, FDA and WHO.
The most critical evaluation is that of biological function, through assays that replicate the likely mechanism of action in vivo, with ADCC assessments forming an important component.
There are strict requirements to show comparability between innovator drugs and biosimilars. ADCC evaluation studies are an essential part of the comparability profile. It is generally accepted that the innovator and biosimilar will be different due to the complex nature of the production process. However, the regulatory approach is that the compounds must be shown to be sufficiently similar to provide the same clinical outcome when used to treat disease.
Our iLite® experts are ready to provide guidance at every step of your project.