T-cell receptor on EGFRvIII-specific CD8+ T cells (EGFRvIII-specific TCR)

The T-cell receptor (TCR) on EGFRvIII-specific CD8+ T cells is a specialized immune receptor engineered or naturally selected to recognize the Epidermal Growth Factor Receptor variant III (EGFRvIII), a tumor-specific neoantigen (PubMed: 25646017). EGFRvIII results from an in-frame deletion of exons 2 through 7 of the EGFR gene, creating a unique glycine residue at the fusion junction that is entirely absent in normal human tissues (PubMed: 25646017). This TCR specifically binds to the EGFRvIII peptide sequence when presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01, on the surface of malignant cells (PubMed: 25646017). In therapeutic contexts, such as TCR-T cell therapy, patient T cells are modified to express this TCR to target and eliminate tumors like glioblastoma multiforme (NCT02458911). Upon binding to its cognate antigen, the TCR triggers a signaling cascade that leads to T-cell proliferation, the secretion of pro-inflammatory cytokines, and the direct lysis of the cancer cell (PubMed: 25646017). While this approach offers high specificity, clinical challenges include tumor heterogeneity and the potential for antigen escape where the tumor loses EGFRvIII expression (PubMed: 28723501).

Other names

EGFRvIII-targeted TCREGFRvIII-specific T-cell receptorEpidermal growth factor receptor variant III-specific TCREGFRvIII-restricted TCR

Recognition of the EGFRvIII neoantigen peptide presented by HLA-A*02:01 on the surface of tumor cells, leading to T-cell activation and cytotoxic destruction of the target cell.