Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas

J Clin Invest. 2007 Feb;117(2):346-52. doi: 10.1172/JCI30446. Epub 2007 Jan 25.


Activating EGFR mutations occur in human non-small cell lung cancer (NSCLC), with 5% of human lung squamous cell carcinomas having EGFRvIII mutations and approximately 10%-30% of lung adenocarcinomas having EGFR kinase domain mutations. An EGFR-targeting monoclonal antibody, mAb806, recognizes a conformational epitope of WT EGFR as well as the truncated EGFRvIII mutant. To explore the anticancer spectrum of this antibody for EGFR targeted cancer therapy, mAb806 was used to treat genetically engineered mice with lung tumors that were driven by either EGFRvIII or EGFR kinase domain mutations. Our results demonstrate that mAb806 is remarkably effective in blocking EGFRvIII signaling and inducing tumor cell apoptosis, resulting in dramatic tumor regression in the EGFRvIII-driven murine lung cancers. Another EGFR-targeting antibody, cetuximab, failed to show activity in these lung tumors. Furthermore, treatment of murine lung tumors driven by the EGFR kinase domain mutation with mAb806 also induced significant tumor regression, albeit to a less degree than that observed in EGFRvIII-driven tumors. Taken together, these data support the hypothesis that mAb806 may lead to significant advancements in the treatment of the population of NSCLC patients with these 2 classes of EGFR mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Apoptosis
  • Cetuximab
  • Cyclin-Dependent Kinase Inhibitor p16 / deficiency
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • ErbB Receptors / immunology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutation*
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / therapy
  • Phosphorylation


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cyclin-Dependent Kinase Inhibitor p16
  • epidermal growth factor receptor VIII
  • ErbB Receptors
  • Cetuximab