title: Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.
abstract: Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.
authors.affiliation: a Department of Surgery , Medical University of Vienna , Vienna , Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: a Department of Surgery , Medical University of Vienna , Vienna , Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rath
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology; D000961:Antilymphocyte Serum / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D007074:Immunoglobulin G; C000609138:avelumab
keywords: Avelumab; antibody-dependent cytotoxicity; immune checkpoints; programmed death ligand-1