Epidermal growth factor receptor (EGFR) extracellular domain D2C7 epitope (EGFR D2C7 epitope)

The Epidermal growth factor receptor (EGFR) extracellular domain D2C7 epitope is a specific conformational site shared by both the wild-type EGFR (wtEGFR) and its type III variant (EGFRvIII) (Chandramohan et al., 2013, PMID: 23471972). This epitope is of significant therapeutic interest because EGFRvIII is a tumor-specific mutation frequently found in glioblastoma, while wtEGFR is often overexpressed in the same tumors (Bigner et al., 2013). The D2C7 monoclonal antibody was specifically engineered to recognize this shared region, allowing for a broader targeting strategy than antibodies specific to only one form of the receptor (Desjardins et al., 2016, PMID: 27613446). In clinical applications, D2C7 is often conjugated to toxins, such as Pseudomonas exotoxin A (forming D2C7-IT), to selectively kill cancer cells through receptor-mediated endocytosis (Sampson et al., 2017). This dual-targeting approach aims to overcome the heterogeneity of EGFR expression in high-grade gliomas, where cells may express wtEGFR, EGFRvIII, or both (Chandramohan et al., 2019, PMID: 31142658). Research indicates that targeting this epitope can effectively inhibit tumor growth and improve survival in preclinical models of malignant glioma.

Other names

D2C7 shared epitopeEGFR/EGFRvIII shared conformational epitopeD2C7-reactive epitope

The D2C7 antibody binds to a specific conformational epitope on the extracellular domain of both wild-type EGFR and the EGFRvIII mutant. Upon binding, the complex is internalized via receptor-mediated endocytosis, allowing for the delivery of cytotoxic payloads like Pseudomonas exotoxin A, which catalyzes the ADP-ribosylation of elongation factor-2, inhibiting protein synthesis and inducing apoptosis (Chandramohan et al., 2013, PMID: 23471972). Alternatively, the epitope serves as a target for CAR T-cell mediated direct cytotoxicity against tumor cells (Sampson et al., 2017).