The FcγRIIIA (CD16) L48-H/R Polymorphism Enhances NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity by Promoting Serial Killing.

ABSTRACT: Many tumor-specific monoclonal antibody therapies stimulate antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells through FcγRIIIa (CD16). The efficacy of these ADCC-based immunotherapies is potentiated in patients with the common CD16 polymorphic variant F158-V that increases the binding affinity between the receptor and the IgG Fc domain. However, other CD16 variants are less well characterized. Here, we report that CD16 L48-H and L48-R variants both significantly enhance in vitro ADCC responses in primary NK cells and NK-92 cells. During ADCC responses, NK cells expressing CD16 48-H killed and disengaged from target cells faster than those expressing CD16 48-L, resulting in improved serial killing of tumor cells. We found that CD16 48-H also formed an immunologic

SUBMITTER: Maskalenko NA 

PROVIDER: S-EPMC11879761 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature