Epidermal growth factor receptor variant III (EGFRvIII) peptide-MHC complex (EGFRvIII-pMHC)

The Epidermal growth factor receptor variant III (EGFRvIII) peptide-MHC complex is a tumor-specific neoantigen target primarily utilized in the development of immunotherapies for glioblastoma multiforme. EGFRvIII is a common mutation resulting from an in-frame deletion of exons 2-7 of the EGFR gene, which creates a unique glycine residue at the fusion junction of exons 1 and 8 (Sampson et al., 2017). This mutation is entirely absent in normal tissues, making the resulting junctional peptide, when presented by Major Histocompatibility Complex (MHC) molecules, an ideal target for high-specificity immune intervention. Therapeutic approaches include peptide vaccines like Rindopepimut, which are designed to be taken up by antigen-presenting cells (APCs) to prime the immune system, as well as T-cell receptor (TCR)-engineered T cells that directly recognize the complex on tumor cells (Schuster et al., 2015). Despite the high specificity of this target, clinical trials have faced challenges such as antigen escape, where tumors recur without the EGFRvIII mutation, and the inherent immunosuppressive environment of the brain (O'Rourke et al., 2017).

Other names

EGFRvIII neoantigen-HLA complexPEPvIII-MHC complexEGFRvIII-derived peptide-MHC class I complexEGFRvIII junctional peptide-HLA-A*02:01 complex

Induction of a tumor-specific cytotoxic T-lymphocyte response through the presentation of the unique EGFRvIII junctional neoepitope by MHC molecules on the surface of antigen-presenting cells and tumor cells.