Nimotuzumab: beyond the EGFR signaling cascade inhibition

Semin Oncol. 2018 Jan;45(1-2):18-26. doi: 10.1053/j.seminoncol.2018.04.008. Epub 2018 May 2.

Abstract

One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades that promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agents are able to induce T-cell activation, transforming a passive therapy into a vaccine-like effect. Nimotuzumab is an IgG1 humanized monoclonal antibody directed against the extracellular domain of the EGFR blocking the binding to its ligands. It possesses unique pharmacodynamic properties, which allow treating patients for long-term periods and with very low toxicity. Based on its clinical effect, nimotuzumab has been approved in Cuba and abroad for the treatment of different epithelial tumors. Recently, new potential mechanisms of action of nimotuzumab involving the activation of the innate and adaptive immune response have been reported. This review summarizes the main properties of nimotuzumab in comparison with other EGFR-specific monoclonal antibodies, highlighting its capacity to activate an effective immune response. In addition, differential clinical effects of this antibody and ongoing clinical trials to deeply characterize the biomarkers of clinical benefit are shown.

Keywords: EGFR; HLA class I molecules; T cells; antibody-dependent cell mediated cytotoxicity (ADCC); monoclonal antibodies; natural killer cells.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antineoplastic Agents, Immunological / immunology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Dendritic Cells / immunology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology
  • Humans
  • Killer Cells, Natural / immunology
  • Models, Immunological
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • nimotuzumab
  • ErbB Receptors