Targeted therapy of solid tumors by monoclonal antibody specific to epidermal growth factor receptor.

Abstract

Tumor growth and progression depends largely on the activity of cell membrane receptors like epidermal growth factor receptor (EGFR) that plays a pivotal role in the progression and invasion of different solid tumors. As one of the most promising approaches for targeting and therapy, monoclonal antibodies (mAbs) have widely been used in the treatment of various malignancies. However, the clinical effects of mAbs appear to be dependent upon its specificity and potency. In the current investigation, a series of mAbs were produced against human EGFR using hybridoma technology. Balb/c mice were immunized against EGFR-positive A431 cancer cells and the most immune mouse was selected for fusion and generation of anti-EGFR mAbs. Isotyping of the generated mAbs was performed by ELISA method. Of various monoclones produced, IgG1 subclass (mAb BF4) displayed specific binding to the EGFR-expressing A431 cells. Flow cytometry and immunofluorescence staining revalidated its specific reactivity with EGFR and MTT assay revealed significant growth inhibition of A431 cells treated with mAb BF4 mainly through induction of apoptosis. Based on these findings, we propose the produced anti-EGFR mAb BF4 to be exploited for diagnostic and possibly treatment of various malignancies with overexpression of EGFR.