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
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
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