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.
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.
García
Beatriz
B
Center of Molecular Immunology, Clinical Imunology Department, Havana, Cuba. beatriz@cim.sld.cu
Neninger
Elia
E
de la Torre
Ana
A
Leonard
Idrissa
I
Martínez
Rocío
R
Viada
Carmen
C
González
Gisela
G
Mazorra
Zaima
Z
Lage
Agustín
A
Crombet
Tania
T
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
D000906:Antibodies; D019496:Cancer Vaccines; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors