Predicting Antibody-Dependent Cell-Mediated Cytotoxicity

By Ethan Shelkey, Scott Kelsey, Aurita Menezes, and Anshika Sharma

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is an immune response where epitope-specific antibodies bind to target cells, such as pathogen-infected or tumor cells. These antibodies are then bound by innate immune effector cells, like natural killer (NK) cells, which initiate cell elimination. A key factor influencing ADCC is a single nucleotide polymorphism (SNP) at position 158 within the NK cell CD16 surface receptor. Individuals with the 158V allele exhibit increased antibody binding potential and higher NK cell ADCC activity.

Therapeutic applications of ADCC are challenging due to individual variations in NK cell cytotoxicity. To address this, Lonza developed a dual screening procedure to identify donors with high ADCC potential. Genotypic screening identified donors as 158F/158F, 158V/158F, or 158V/158V. Phenotypic screening assessed NK cell population size and CD16 expression via flow cytometry.

By combining genotypic and phenotypic characterization, researchers can choose PBMC donors that best fit their needs. This includes selecting donors with high ADCC potential for early drug discovery screening, donor diversity for predicting ADCC-focused immunotherapeutic outcomes, rescuing ADCC response in low-affinity PBMC donors, or testing a range of responders to replicate population dynamics.