Mutant Epidermal Growth Factor Receptor neoantigen peptide–Major Histocompatibility Complex class I complex (Mutant EGFR-pMHC)

Mutant Epidermal Growth Factor Receptor (EGFR) neoantigen peptide–Major Histocompatibility Complex (MHC) class I complexes are tumor-specific targets formed when mutated EGFR proteins are processed into peptides and presented on the cell surface by HLA molecules (Source: PubMed ID: 33859014). These complexes are highly prevalent in cancers such as non-small cell lung cancer (NSCLC), where the L858R mutation is common, and glioblastoma, which often expresses the EGFRvIII variant (Source: Journal of Hematology & Oncology, 2021). The biological role of these complexes is to serve as flags for the immune system, allowing CD8+ T cells to recognize and eliminate malignant cells through their T-cell receptors (TCRs). Because these neoantigens are absent in normal tissues, they represent ideal targets for precision immunotherapies, including TCR-engineered T-cell (TCR-T) therapies and neoantigen-based vaccines (Source: Nature Communications, 2021). Current drug development focuses on identifying high-affinity TCRs or bispecific antibodies that can bind these specific pMHC complexes without cross-reacting with wild-type EGFR peptides presented on healthy cells. However, therapeutic challenges include the potential for HLA downregulation by tumors to evade immune detection and the high degree of HLA polymorphism among patients (Source: Frontiers in Immunology, 2022). Successful targeting of these complexes could provide a potent and highly selective treatment option for patients with EGFR-mutated malignancies who have failed traditional tyrosine kinase inhibitor therapies.

Other names

EGFR neoantigen-HLA complexMutant EGFR peptide-MHC complexEGFRvIII-MHC complexEGFR L858R-HLA-A*02:01 complexEGFR-derived neoantigen-pMHC

Therapeutic agents specifically recognize the mutant EGFR peptide presented within the MHC class I groove, triggering T-cell mediated cytotoxicity against the tumor cell (Source: Nature Communications, 2021).