title: Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by anti-epidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor cancer vaccine.
abstract: OBJECTIVE
  Epidermal growth factor (EGF) might be a suitable immunotherapeutic target in non-small-cell lung cancer (NSCLC). Our approach consists of active immunotherapy with EGF. The aim of the study is to characterize the humoral response and its effects on signal transduction in relation with the clinical outcome.
  
  
  METHODS
  Eighty NSCLC patients treated with first-line chemotherapy were randomized to receive the EGF vaccine or supportive care. EGF concentration in sera, anti-EGF antibodies and their capacity to inhibit the binding between EGF/EGF receptor (EGFR), and the EGFR phosphorylation were measured.
  
  
  RESULTS
  Seventy-three percent of vaccinated patients developed a good antibody response, whereas none of the controls did. In good antibody-responder patients, self EGF in sera was significantly reduced. In 58% of vaccinated patients, the post-immune sera inhibited EGF/EGFR binding; in the control group, no inhibition occurred. Post-immune sera inhibited the EGFR phosphorylation whereas sera from control patients did not have this capacity. Good antibody-responder patients younger than 60 years had a significantly better survival. A high correlation between anti-EGF antibody titers, EGFR phosphorylation inhibition, and EGF/EGFR binding inhibition was found. There was a significantly better survival for vaccinated patients that showed the higher capacity to inhibit EGF/EGFR binding and for those who showed an immunodominance by the central region of EGF molecule.
  
  
  CONCLUSIONS
  Immunization with the EGF vaccine induced neutralizing anti-EGF antibodies capable of inhibiting EGFR phosphorylation. There was a significant positive correlation between antibody titers, EGF/EGFR binding inhibition, immunodominance of anti-EGF antibodies, and survival in advanced NSCLC patients.
authors.affiliation: Center of Molecular Immunology, Clinical Imunology Department, Havana, Cuba. beatriz@cim.sld.cu
authors.forename: Beatriz
authors.initials: B
authors.lastname: García
authors.forename: Elia
authors.initials: E
authors.lastname: Neninger
authors.forename: Ana
authors.initials: A
authors.lastname: de la Torre
authors.forename: Idrissa
authors.initials: I
authors.lastname: Leonard
authors.forename: Rocío
authors.initials: R
authors.lastname: Martínez
authors.forename: Carmen
authors.initials: C
authors.lastname: Viada
authors.forename: Gisela
authors.initials: G
authors.lastname: González
authors.forename: Zaima
authors.initials: Z
authors.lastname: Mazorra
authors.forename: Agustín
authors.initials: A
authors.lastname: Lage
authors.forename: Tania
authors.initials: T
authors.lastname: Crombet
mesh_terms: D000906:Antibodies / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality; D018579:Patient Selection; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000276:immunology; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors