Epidermal growth factor receptor tumor-associated epitopes (EGFRvIII/mAb806)

The Epidermal Growth Factor Receptor (EGFR) tumor-associated epitopes, primarily EGFRvIII and the mAb806-defined conformational epitope, are distinct structural motifs found almost exclusively on malignant cells. EGFRvIII is a common mutation in glioblastoma characterized by the deletion of exons 2-7, resulting in a truncated extracellular domain that signals constitutively without ligand binding (Gan et al., 2013, PMID: 23414956). The mAb806 epitope is a cryptic sequence (amino acids 287-302) that is exposed in EGFRvIII and in overexpressed wild-type EGFR when it adopts an untethered conformation, but remains hidden in the tethered state of normal wild-type EGFR (Johns et al., 2002, PMID: 11830592). These epitopes allow for the development of therapies that selectively target tumor cells while sparing normal tissues that express wild-type EGFR, such as the skin and gastrointestinal tract. Therapeutic approaches include antibody-drug conjugates like depatuxizumab mafodotin, vaccines like rindopepimut, and CAR-T cell therapies (Lassman et al., 2017, PMID: 28339594). Despite their promise, challenges such as intratumoral heterogeneity and antigen escape remain significant hurdles in clinical application (O'Rourke et al., 2017, PMID: 28724573).

Other names

EGFRvIIIde2-7 EGFREGFR variant IIImAb 806 epitopeCH12 epitopeABT-414 epitopeEpidermal growth factor receptor variant III

Targeted delivery of cytotoxic payloads via antibody-drug conjugates, induction of antibody-dependent cellular cytotoxicity (ADCC), inhibition of constitutive ligand-independent signaling, and T-cell mediated tumor cell lysis.