Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells

Cancer Immunol Res. 2015 Oct;3(10):1148-1157. doi: 10.1158/2326-6066.CIR-15-0059. Epub 2015 May 26.


Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / genetics
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • Antineoplastic Agents / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Gene Expression
  • Genotype
  • Humans
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-12 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Receptors, IgG / genetics
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • FCGR3A protein, human
  • Receptors, IgG
  • Interleukin-12
  • Interferon-gamma
  • avelumab