Mutant Epidermal Growth Factor Receptor-derived neoantigen peptide-HLA complex (Mutant EGFR-neoAg-HLA)

Mutant Epidermal Growth Factor Receptor (EGFR)-derived neoantigen peptides presented by Human Leukocyte Antigen (HLA) molecules are tumor-specific antigens arising from somatic mutations in the EGFR gene, such as L858R, T790M, and the EGFRvIII deletion. These mutations are prevalent in non-small cell lung cancer (NSCLC) and glioblastoma, where they act as oncogenic drivers. The mutated proteins are processed into peptides and presented on the cell surface by HLA class I or II molecules, forming a complex that can be recognized by T-cell receptors (TCRs). This recognition triggers an adaptive immune response, specifically activating CD8+ and CD4+ T cells to eliminate tumor cells. Therapeutic interventions targeting these complexes include personalized neoantigen vaccines, such as Rindopepimut (CDX-110), and TCR-engineered T-cell (TCR-T) therapies. Because these neoantigens are absent in healthy tissues, they provide a high degree of specificity, potentially minimizing off-target effects. However, clinical efficacy can be hindered by immune evasion mechanisms like HLA loss of heterozygosity (LOH) or mutations in the antigen presentation machinery, such as B2M.

Other names

Mutant EGFR-derived neoantigen peptides presented by HLAEGFR neoepitope-HLA complexEGFR pMHC complexEGFRvIII neoantigenEGFR L858R neoantigenEGFR T790M neoantigenEGFR Exon 19 deletion neoantigen

T-cell receptor-mediated recognition of the peptide-HLA complex leading to T-cell activation and tumor cell lysis.