The cell adhesion protein CD56 has been identified as a potential therapeutic target in several solid tumors and hematological malignancies. Recently, we developed a CD56-directed antibody-drug conjugate (ADC), called Adcitmer and demonstrated its antitumor properties in preclinical models of the rare and aggressive skin cancer Merkel cell carcinoma (MCC).The present study aims to further optimize Adcitmer to overcome the therapeutic limitations observed with previously evaluated CD56-targeting ADCs, which were partially related to toxic effects on leukocytes. To this end, we aimed to avoid interaction of Adcitmer with immune cells via Fc gamma receptor (FcγR) binding. Since glycosylation is essential for FcγR binding, an aglycosylated form of Adcitmer was generated and evaluated on human leukocytes and MCC cell lines using cell death (annexin V/