%0 Journal Article
%T Immunohistochemical Characterization of Three Monoclonal Antibodies Raised against the Epidermal Growth Factor and Its Receptor in Non-Small-Cell Lung Cancer: Their Potential Use in the Selection of Patients for Immunotherapy
%A Charles E. Rengifo
%A Ranc¨¦s Blanco
%A Dami¨˘n Blanco
%A Mercedes CedeŁżo
%A Milagros Fr¨®meta
%A Enrique Rengifo Calzado
%J Journal of Biomarkers
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/627845
%X Adequate methods to identify which lung cancer patients are most likely to benefit from the targeted drugs against both epidermal growth factor receptor/epidermal growth factor (EGFR/EGF) are needed. For this reason, we evaluated both the tissue reactivity of ior egf/r3 monoclonal antibody (Mab) in human lung carcinomas and its biological activity in NCI-H125 cells. Additionally, we assessed the tissue expression of EGF using two Mabs, CB-EGF1 and CB-EGF2. The overexpression of EGFR was detected in 33.33% and 62.71% of small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), respectively. The ability of ior egf/r3 Mab to bind the extracellular domain of EGFR inhibiting cell proliferation and inducing apoptosis in NCI-H125 cells was also demonstrated. The EGF expression was observed in about 17% and 70% of SCLC and NSCLC, respectively. However, differences in the reactivity of CB-EGF1 and CB-EGF2 were evidenced. A dual expression of EGFR and EGF was observed in 16.67% and 57.63% of SCLC and NSCLC patients, respectively. But, a correlation between them was only obtained in NSCLC. Our results permit to recommend the development of diagnostic kits using ior egf/r3 and/or CB-EGF1 Mabs in order to achieve a better selection of patients to EGFR/EGF-targeting treatment. 1. Introduction Lung cancer is one of the leading causes of cancer-related deaths worldwide [1]. Non-small-cell lung cancer (NSCLC) is the most common form of the disease, accounting for approximately 85% of all cases [2]. In patients with NSCLC, some genetic and regulatory abnormalities have been considered responsible for the tumor survival advantage [3], limiting the survival benefit provided by the standard therapeutic options available. Therefore, drugs targeting abnormal pathways could lead to more effective treatments for this often difficult disease [4]. Since the identification of some alterations in the expression of both epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) in lung cancer pathogenesis, several therapeutic targeting agents have been employed for the treatment of lung tumors overexpressing these molecules [5, 6]. At least three different types of agent for EGF/EGFR inhibition are currently in use: tyrosine kinase inhibitors (TKIs), monoclonal antibodies (Mabs), and molecular cancer vaccines. Among them, nimotuzumab, a humanized therapeutic monoclonal antibody that neutralize the EGFR, and CIMAVax-EGF, a molecular vaccine that induces anti-EGF antibodies neutralizing endogenous EGF, have demonstrated promising results in patients with
%U http://www.hindawi.com/journals/jbm/2013/627845/