Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity

Expert Opin Biol Ther. 2017 Apr;17(4):515-523. doi: 10.1080/14712598.2017.1294156. Epub 2017 Feb 22.


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.

Keywords: Avelumab; antibody-dependent cytotoxicity; immune checkpoints; programmed death ligand-1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antilymphocyte Serum / immunology
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / immunology
  • Cell Cycle Checkpoints / drug effects*
  • Cell Cycle Checkpoints / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Neoplasms / drug therapy
  • Neoplasms / immunology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antilymphocyte Serum
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Immunoglobulin G
  • avelumab