This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by García, B. Articles by Crombet, T. Search for Related Content PubMed PubMed Citation Articles by García, B. Articles by Crombet, T.

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

Authors' Affiliations: ¹ Center of Molecular Immunology; ² Hermanos Ameijeiras Hospital, Havana, Cuba; and ³ Celestino Hernández Hospital, Villa Clara, Cuba

Requests for reprints: Beatriz Garcia Verdecia, Clinical Immunology Department, Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba. Phone: 537-271-7933; Fax: 537-272-0644; E-mail: beatriz{at}cim.sld.cu.

Purpose: 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.

Experimental Design: 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.

This article has been cited by other articles:

				J. Fang, Y. Lu, K. Ouyang, G. Wu, H. Zhang, Y. Liu, Y. Chen, M. Lin, H. Wang, L. Jin, et al. Specific Antibodies Elicited by a Novel DNA Vaccine Targeting Gastrin-Releasing Peptide Inhibit Murine Melanoma Growth In Vivo Clin. Vaccine Immunol., July 1, 2009; 16(7): 1033 - 1039. [Abstract] [Full Text] [PDF]

				E. A. Hirschowitz and J. R. Yannelli Immunotherapy for Lung Cancer Proceedings of the ATS, April 15, 2009; 6(2): 224 - 232. [Abstract] [Full Text] [PDF]