Antibody dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody, avelumab (MSB0010718C), on human tumor cells.

3038 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. In addition to disruption of immune suppressive signaling induced by the binding of PD-L1 on tumor cells with PD-1 on tumor infiltrating immune cells, avelumab was designed to mediate antibody dependent cellular cytotoxicity (ADCC). Other anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) undergoing clinical evaluation are either of the IgG1 isotype and modified to remove ADCC activity or of the IgG4 isotype, which does not mediate ADCC. We present data from preclinical studies examining the ability of avelumab to induce ADCC and factors affecting tumor cell sensitivity to this mechanism. Methods: The ability of avelumab to induce lysis of human carcinoma cells was assessed using whole peripheral blood mononuclear cells (...