Enhanced Fc and complement activity of Fc‐modified avelumab boosts anti‐tumor activity but promotes <scp>NK</scp> cell fratricide

Objectives: NK cells. However, subsets of patients possess lower-affinity CD16a allotypes that limit ADCC capacity of monoclonal antibodies. In this study, we modified the Fc domain of avelumab with characterised mutations to enhance ADCC across all CD16a allotypes. Methods: target cells were coated with mab prior to incubation with effector cells, with both high- and low-affinity CD16a allotypes represented. Human serum was employed for assessing CDC. Results: lymphoma cell line. However, short term activation of NK cells or long-term expansion on artificial antigen presenting cells, led to upregulation of PD-L1 on NK cells. Addition of avelumab or AveFc5M to these NK cell populations induced a marked reduction in viable NK cells via ADCC-mediated fratricide. Conclusion: tumors. However, the enhanced effector function of AveFc5M led to NK cell fratricide, potentially limiting NK cell-dominated anti-cancer responses.