BioOutsource has the experience, expertize and capabilities to provide complete Antibody-Dependent Cell Mediated-Cytotoxicity (ADCC) testing solutions for your biologic product. We provide a comprehensive service offering for measurement of the ADCC activity of therapeutic antibodies. Our highly qualified scientist have extensive experience in the development, optimization and qualification of ADCC assays across different antibody products, utilizing a range of different assay endpoints. Depending upon your requirements, our ADCC assays can be performed using PBMCs from a variety of genotyped donors that are specifically harvested on the day of assay. Our ADCC assay portfolio also includes the use of a surrogate ADCC assay which uses an engineered cell line stably expressing the FcgRIIIa receptor to negate donor-specific variability. We offer a range of Fc Receptor binding assays to complement our functional ADCC assays in the characterization of your product.
ADCC Mechanism of Action
ADCC is part of the adaptive immune system’s defense mechanism to remove infected or cancerous cells. Marketed monoclonal antibody products such as Herceptin and Rituxan mediate their activity through the induction of cancer cell death via ADCC mechanisms, and other antibodies such as Erbitux, Humira and Remicade have the potential to mediate ADCC activity as secondary or tertiary mechanisms of action. Increasingly, monoclonal antibody products are being designed to remove or limit the ADCC activity of the molecule and whilst other marketed products such as Avastin are reported to have no ADCC activity. Determination of the presence of ADCC activity and subsequent quantification of ADCC activity, if present, is a critical step in the development and characterization of therapeutic antibodies. The glycosylation pattern of the antibodies can also have a significant effect on ADCC activity and variation in the production process can also lead to variable levels of ADCC of an antibody; functional and surrogate ADCC assays can therefore play a pivotal role in optimization of the manufacturing process.
As with all bioassays, ADCC assays are intended to provide a measure of the biological activity of the drug, but these methods are complicated by the complexity of the ADCC process; the effector functions are mediated by the patient and this creates an external variable that should be considered during development of ADCC methods. The ADCC process is mediated by the Fc-gamma Receptor IIIa (FcRIIIa/CD16a) which is expressed by natural killer cells and functions to recognize and bind the Fc portion of IgG antibodies. Two distinct allelic variations exist for this receptor giving rise to three different genotypes (V/V, F/F, V/F) each with different affinities for IgG and clinical differences have been reported between patients of different genotypes. The results obtained from ADCC assays can also be affected by different PBMCs obtained from donors of differing genotypes. As part of early phase ADCC evaluation, therapeutic monoclonals should be evaluated against a battery of donors with different genotypes.
The requirement to evaluate ADCC activity of therapeutic antibodies is based upon a number of considerations, but is primarily governed by the primary mechanism of action of the drug, however a risk based approach should be applied to determine if possible secondary ADCC mechanism of action may arise. It may also be appropriate to demonstrate the absence of ADCC and BioOutsource offers a standardized, highly robust approach for the difficult task of formally demonstrating a negative result.
Contact our experts today to discuss outsourcing ADCC assays with BioOutsource.
ADCC Testing for Biosimilars
BioOutsource offer a suite of off-the-shelf ADCC assays for a range of biosimilar molecules. Learn more about the importance of accurately determining ADCC activity for biosimilar monoclonal antibodies in our video: