Epidermal growth factor receptor epitope 806 (EGFR806)

Epidermal growth factor receptor (EGFR) epitope 806 is a cryptic, conformational epitope located within the extracellular domain of the EGFR protein, specifically encompassing amino acids 287 to 302 (aacrjournals.org). This epitope is uniquely accessible when the receptor is in an untethered or active conformation, a state predominantly found in cells with EGFR gene amplification, protein overexpression, or the EGFRvIII mutation (nih.gov). Because the epitope is hidden in the tethered, inactive conformation of wild-type EGFR on normal tissues, it serves as a highly tumor-specific target for therapeutic intervention (nih.gov). Monoclonal antibodies like mAb 806 and its humanized version ABT-806, as well as antibody-drug conjugates like depatuxizumab mafodotin, have been developed to exploit this specificity (researchgate.net). Additionally, epitope 806 is a primary target for next-generation chimeric antigen receptor (CAR) T-cell therapies, particularly in the treatment of glioblastoma (clinicaltrials.gov). These therapeutic approaches aim to disrupt oncogenic signaling and induce targeted cell death while sparing normal tissues from the typical toxicities associated with pan-EGFR inhibition (nih.gov).

Other names

mAb 806 epitopeCryptic EGFR epitopeTumor-specific EGFR epitopeEGFRvIII-associated epitope

Drugs targeting EGFR epitope 806 bind specifically to the exposed conformational epitope on overexpressed or mutated EGFR, such as the EGFRvIII variant (aacrjournals.org). Monoclonal antibodies and antibody-drug conjugates (ADCs) inhibit ligand-independent receptor activation, promote receptor internalization, and deliver cytotoxic payloads or induce antibody-dependent cellular cytotoxicity (ADCC) (nih.gov). Chimeric antigen receptor (CAR) T-cells recognize the epitope to trigger T-cell activation, leading to the release of cytotoxic granules like perforin and granzymes, as well as pro-inflammatory cytokines (e.g., IFN-gamma, TNF-alpha) that mediate tumor cell lysis (nih.gov, clinicaltrials.gov).