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.

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy

“…Presence of specific homing ligands, attached on the surface of nanosystem and enabling active binding with receptors overexpressed on tumor cells represent a standard model of active drug delivery strategy. A number of molecules, including transferrin-receptors (TfR), epidermal growth factor receptors (EGFR), folate receptors (FR), CD44 or CD22 can be engaged in this manner [ 34 , 44 – 47 ]. Accordingly, tumor-specific ligands interact with receptors on the surface of cancer tissues, triggering receptor-mediated endocytosis and internalization of nanoparticle into cancer cells [ 48 ].…”

Recent advances in targeted therapy of colorectal cancer: impacts of monoclonal antibodies nanoconjugates

“…VEGF and EGFR are two key molecular markers and receptors in the growth and dissemination of tumors especially CRC. 13,14 EGFR expression has been observed in almost 70% of human colorectal carcinomas 15 and VEGF is minimally expressed in approximately 50% of CRCs. However, these receptors have a comparatively lower expression in normal colonic mucosa and adenomas.…”